Oxime derivatives, hydrazone derivatives and use thereof

ABSTRACT

Compounds having fungicidal activities and represented by general formula (I) and salts and hydrates thereof                    
     wherein R 1  represents an optionally substituted aryl, an optionally substituted alkyl or the like; R 2  represents an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted aryl, an optionally substituted heterocyclic group or the like; R 3  represents an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted arylsulfonyl, an optionally substituted heterocyclic group or the like; R 4  and R 5 , which may be the same or different, represent each a hydrogen atom, an optionally substituted alkyl, or an optionally substituted alkoxy, or R 4  and R 5  may form together with the adjacent nitrogen atom an optionally substituted monocycle or polycycle; X and Y, which may be the same or different, represents each an oxygen atom or NR 6  wherein R 6  represents a hydrogen atom, an optionally substituted alkyl, an optionally substituted aryl, an optionally substituted alkanoyl, or an optionally substituted aroyl; Z represents an oxygen atom or a sulfur atom; and a wavy line (˜) represents the configuration of an E isomer, a Z isomer, or a mixture thereof.

This application is a divisional of U.S. application Ser. No. 09/284,239 filed Apr. 14, 1999, U.S. Pat. No. 6,096,741, which was filed as International Application No. PCT/JP97/03585 filed Oct. 7, 1997.

TECHNICAL FIELD

The present invention relates to a novel oxime derivative and a novel hydrazone derivative as well as the use of the same.

BACKGROUND ART

While as oxime derivatives and hydrazone derivatives analogous to the present invention Japanese Patent Application Laid-Open Nos. 3-215464 and 7-309825, and WO 95/21153, WO 95/21154, WO 95/18789 and WO 96/11183 disclose compounds having fungicidal activities, a compound disclosed in the present invention is not included in these publications. In addition, none of these publications mentioned the tachykinin receptor antagonism of the compounds disclosed therein.

Tachykinin is a name which is used commonly in a group of the neuropeptides having 10 to 11 amino acids, and includes substance P, neurokinin A and neurokinin B which are known. Each of these substances binds to three receptors, namely NK1, NK2 and NK3, and is known to be involved in pain transmission, vasodilation, saliva secretion, increase in capillary vessel permeability, immunoregulation, nerve cell regulation and the like. Accordingly, a compound having a tachykinin receptor antagonistic effect is considered to have various biological activities, and each of EP 394989, EP 428434, EP 429366, EP 436334, EP 443132, EP 474561, EP 482 539, EP 499313, EP 512901, EP 512902, EP 514273, EP 514275, EP 515240, EP 517589, EP 520555, EP 522808, EP 528495, EP 532456, EP 533280, EP 536817, EP 545478, EP 559538, EP 585913, WO 90/05525, WO 90/05729, WO 91/09844, WO 91/18899, WO 92/01688, WO 92/06079, WO 92/12151, WO 95/15585, WO 92/19254, WO 92/20661, WO 92/20667, WO 93/00330, WO 93/00331, WO 93/01159, WO 93/01165, WO 93/01169, WO 93/01170, WO 93/06099, WO 93/09116, WO 93/10073, WO 93/14084, WO 93/18023, WO 93/19064, WO 93/21155, WO 93/21181, WO 93/23380, WO 94/16697, WO 94/17045, WO 94/19323, WO 94/20500, WO 94/26740, WO 94/29309, WO 95/02595, WO 95/04040, WO 95/04042, WO 95/18124, WO 95/18129, WO 95/28389, WO 96/29326, WO 96/30367, Japanese Patent Application Laid-Open Nos. 8-239323, 8-295667, 8-2301849 and 8-301871 discloses a compound having a tachykinin receptor antagonistic effect.

However, none of these publications describes an oxime derivative or a hydrazone derivative disclosed in the present invention.

DISCLOSURE OF INVENTION

An objective of the present invention is to provide a compound having a higher fungicidal effect and a higher tachykinin receptor antagonistic effect.

The present inventors made an effort to achieve the objective described above and finally found that a novel oxime derivative and a novel hydrazone derivative described below have a higher fungicidal effect and a higher tachykinin receptor antagonistic effect, whereby accomplishing the present invention.

Thus, the present invention is a compound represented by Formula (I):

wherein R¹ is an optionally substituted aryl, an optionally substituted alkyl or an optionally substituted cycloalkyl; R² is an optionally substituted alkyl, an optionally substituted cycloalkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted alkylsulfonyl, an optionally substituted aryl, an optionally substituted arylsulfonyl or an optionally substituted heterocyclic group; R³ is an optionally substituted alkyl, an optionally substituted cycloalkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted alkylsulfonyl, an optionally substituted aryl, an optionally substituted arylsulfonyl or an optionally substituted heterocyclic group; R⁴ and R⁵ are the same or different from each other and each is a hydrogen atom, an optionally substituted alkyl, an optionally substituted cycloalkyl or an optionally substituted alkoxy, or R⁴ and R⁵ may be taken together with their adjacent nitrogen atom to form an optionally substituted monocyclic ring or polycyclic ring; X and Y are the same or different from each other and each is an oxygen atom or an NR⁶ wherein R⁶ is a hydrogen atom, an optionally substituted alkyl, an optionally substituted aryl, an optionally substituted alkanoyl or an optionally substituted aroyl; Z is an oxygen atom or a sulfur atom; a wave-shaped line (˜) represents the configuration of a E form or a Z form or a mixture thereof;

provided that when R² is an optionally substituted benzyl, then the substituent is not a group represented by formula:

 wherein (R¹²)₂ is H₂, ═O, ═CH—OH, ═CHOCH₃, ═N—OH or ═N—OCH₃; and R¹³ represents an alkoxy or a monoalkylamino;

and a salt or a hydrate thereof preferably a compound or a salt or a hydrate thereof described above wherein R¹ is an aryl or an alkyl; R² is an optionally substituted alkyl, alkenyl, alkynyl, aryl or heterocyclic group; R³ is an optionally substituted alkyl, alkenyl, alkynyl, an optionally substituted aryl, an optionally substituted arylsulfonyl or heterocyclic group; R⁴ and R⁵ are the same or different from each other and each is a hydrogen atom, an alkyl or an alkoxy, or R⁴ and R⁵ may be taken together with their adjacent nitrogen atom to form an optionally substituted monocyclic ring; X and Y are the same or different from each other and each is an oxygen atom or a NR⁶ wherein R⁶ is a hydrogen atom, alkyl, aryl, alkanoyl or aroyl.

BEST MODE FOR CARRYING OUT THE INVENTION

In this specification, the term “lower” means a straight or branched chain group having 1 to 8 carbon atoms, preferably 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms, unless otherwise specified.

The aryl in an optionally substituted aryl represented by R¹ may be an aryl having 6 to 14 carbon atoms, such as phenyl, naphthyl (e.g., 1-naphthyl, 2-naphthyl) and the like.

The substituent on an optionally substituted aryl represented by R¹ may for example be a lower alkyl (e.g., methyl, ethyl, propyl, butyl and the like), a lower alkenyl (e.g., vinyl, allyl, 2-butenyl and the like), a lower alkynyl (e.g., ethynyl, 2-propynyl, 3-butynyl and the like), a cycloalkyl (e.g., cyclopropyl, cyclopentyl, cyclohexyl and the like), a cycloalkenyl (e.g., cyclopentenyl, cyclohexenyl and the like), a halogenated lower alkyl (e.g., trifluoromethyl, trichloromethyl, difluoromethyl, chloromethyl, 2-bromoethyl, 1,2-dichloropropyl and the like), a halogen atom (e.g., fluorine atom, chlorine atom, bromine atom, iodine atom), nitro, cyano, a lower alkylthio (e.g., methylthio, ethylthio, propylthio and the like), —NR⁸R⁹ wherein R⁸ and R⁹ are the same or different from each other and each is a hydrogen atom, an optionally substituted lower alkyl (e.g., methyl, ethyl, propyl, 2-chloroethyl, methoxymethyl, 2-ethoxyethyl, benzyl, 4-chlorobenzyl, 2-oxopropyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, carbamoylmethyl and the like), formyl, a lower alkanoyl (e.g., acetyl, propionyl and the like), a lower alkoxycarbonyl (e.g., methoxycarbonyl, ethoxycarbonyl and the like), an optionally substituted aryl (e.g., phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 1-naphthyl, 2-naphthyl and the like), an optionally substituted aroyl (e.g., benzoyl, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 2-methylbenzoyl, 3-methylbenzoyl, 4-methylbenzoyl, 2-methoxybenzoyl, 3-methoxybenzoyl, 4-methoxybenzoyl and the like), an optionally substituted lower alkylsulfonyl (e.g., methanesulfonyl, ethanesulfonyl, trifluoromethanesulfonyl and the like), an optionally substituted arylsulfonyl (e.g., benzenesulfonyl, 4-chlorobenzenesulfonyl, 4-methylbenzenesulfonyl and the like); or alternatively R⁸ and R⁹ may be taken together to form a cyclic system such as pyrrolidine, piperidine, morpholine, thiomorpholine, piperazine and the like, —OR¹⁰ wherein R¹⁰ is a hydrogen atom, a lower alkyl (e.g., methyl, ethyl, propyl and the like), a lower alkenyl (e.g., vinyl, allyl, 2-butenyl and the like), a lower alkynyl (e.g., ethynyl, 2-propynyl, 3-butynyl and the like), an optionally substituted aryl (e.g., phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 1-naphthyl, 2-naphthyl and the like), an alkoxyalkyl (e.g., methoxymethyl, ethoxymethyl, 2-methoxyethyl and the like), or a lower alkanoyl (e.g., acetyl, propionyl and the like), a lower alkanoyl (e.g., acetyl, propionyl and the like), a lower alkoxycarbonyl (e.g., methoxycarbonyl, ethoxycarbonyl and the like), an optionally substituted aroyl (e.g., benzoyl, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 2-methylbenzoyl, 3-methylbenzoyl, 4-methylbenzoyl, 2-methoxybenzoyl, 3-methoxybenzoyl, 4-methoxybenzoyl and the like), a lower alkylsulfonyl (e.g., mesyl and the like), phenyl, a phenyl(lower)alkyl (e.g., benzyl, phenethyl and the like), a phenyl(lower)alkenyl (e.g., styryl, cinnamyl and the like) and the like. Each of these substituents may be in any possible position on the respective aryl group, and may occur one to four times.

The alkyl in an optionally substituted alkyl represented by R¹ may be a straight or branched chain alkyl having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, and is typically methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl and the like.

The substituent on an optionally substituted alkyl may for example be nitro, cyano, a halogen atom (e.g., fluorine atom, chlorine atom. bromine atom, iodine atom), a cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like), hydroxy, a lower alkoxy (e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy and the like), —NR⁸R⁹ wherein R⁸ and R⁹ are defined as described above, a lower alkylthio (e.g., methylthio, ethylthio, propylthio and the like), a lower alkylsulfonyl (e.g., methanesulfonyl, ethanesulfonyl and the like), an optionally substituted aryl (similar to those exemplified as an optionally substituted aryl represented by R¹ described above), an optionally substituted heterocyclic group (e.g., pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, isoxazol-3-yl, isoxazol-5-yl, pyrrol-2-yl, pyrazol-3-yl, furan-2-yl, furan-3-yl, thiophen-2-yl, thiophen-3-yl, imidazol-2-yl, oxazol-2-yl, thiazol-2-yl and the like), ═O, ═NOR¹¹ wherein R¹¹ is the same or different from each other and a hydrogen atom, a lower alkyl (e.g., methyl, ethyl, propyl and the like), a lower alkenyl (e.g., allyl, 2-butenyl and the like), a lower alkynyl (e.g., 2-propynyl, 3-butynyl and the like), or a lower alkanoyl (e.g., acetyl, propionyl and the like), an optionally substituted aroyl (e.g., benzoyl, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 2-methylbenzoyl, 3-methylbenzoyl, 4-methylbenzoyl, 2-methoxybenzoyl, 3-methoxybenzoyl, 4-methoxybenzoyl and the like), a lower alkoxycarbonyl (e.g., methoxycarbonyl, ethoxycarbonyl and the like), an optionally substituted arylsulfonyl (e.g., benzenesulfonyl, 4-chlorobenzenesulfonyl, 4-methylbenzenesulfonyl and the like) and the like.

The cycloalkyl in an optionally substituted cycloalkyl represented by R¹ may be a cycloalkyl having 3 to 8 carbon atoms, preferably 3 to 6 carbon atoms. Typically, cyclopropyl, cyclopentyl and cyclohexyl may be mentioned.

The substituent on an optionally substituted cycloalkyl represented by R¹ may be similar to those exemplified as the substituent on an optionally substituted alkyl represented by R¹ described above.

R¹ is preferably methyl, ethyl, propyl, isopropyl, optionally substituted phenyl and the like.

Examples of an optionally substituted alkyl represented by R² may be those exemplified as an optionally substituted alkyl represented by R¹ described above.

Examples of an optionally substituted cycloalkyl represented by R² may be those exemplified as an optionally substituted cycloalkyl represented by R¹ described above.

The alkenyl in an optionally substituted alkenyl represented by R² may be an alkenyl having 2 to 6 carbon atoms, preferably 2 to 4 carbon atoms, and is typically 1-propenyl, isopropenyl, allyl, 2-butenyl and the like.

The alkynyl in an optionally substituted alkynyl represented by R² may be an alkynyl having 3 to 6 carbon atoms, preferably 3 to 4 carbon atoms, and is typically 2-propynyl, 3-butynyl and the like.

The alkyl in an optionally substituted alkylsulfonyl represented by R² may be those exemplified as an alkyl represented by R¹ described above.

The substituent on a substituted alkenyl, a substituted alkynyl and a substituted alkylsulfonyl represented by R² may be similar to those exemplified as the substituent on a substituted alkyl represented by R¹ described above.

Examples of an optionally substituted aryl represented by R² may be those exemplified as an optionally substituted aryl represented by R¹ described above.

Examples of an optionally substituted aryl on an optionally substituted arylsulfonyl represented by R² may be those exemplified as an optionally substituted aryl represented by R¹ described above.

An optionally substituted heterocyclic group represented by R² includes a non-substituted heterocyclic group as well as a substituted heterocyclic group. Examples of these heterocyclic groups are a 5- to 7-membered heterocyclic group containing 1 to 4 hetero atoms selected from the group consisting of nitrogen, sulfur and oxygen atoms, and typically, pyridyl (e.g., pyridin-2-yl, pyridin-3-yl, pyridin-4-yl), pyrimidinyl (e.g., pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl), isoxazolyl (e.g., isoxazol-3-yl, isoxazol-5-yl and the like), thiadiazolyl (e.g., 1,3,4-thiadiazol-2-yl, 1,2,3-thiadiazol-4-yl and the like), pyridazinyl (e.g., pyridazin-3-yl, pyridazin-4-yl and the like), pyrrolyl (e.g., pyrrol-l-yl, pyrrol-2-yl and the like), pyrazolyl (e.g., pyrazol-1-yl, pyrazol-3-yl and the like), furyl (e.g., furan-2-yl, furan-3-yl), thienyl (e.g., thiophen-2-yl, thiophen-3-yl), imidazolyl (e.g., imidazol-1-yl, imidazol-2-yl and the like), oxazolyl (e.g., oxazol-2-yl, oxazol-4-yl and the like), thiazolyl (e.g., thiazol-2-yl and the like), oxadiazolyl (e.g., 1,3,4-oxadiazol-2-yl, 1,2,4-oxadiazol-5-yl and the like), pyrazinyl (e.g., pyrazin-2-yl and the like), quinolyl (e.g., quinolin-2-yl and the like) and indolyl (e.g., indolin-1-yl, indolin-2-yl and the like) and the like.

Each of these heterocyclic groups may have a bond in any possible position.

The substituent on a substituted heterocyclic group represented by R² may be similar to those exemplified as the substituent on a substituted allyl represented by R¹ described above. Each of these substituents may be in any possible position on the respective heterocyclic group, and may occur one to three times.

R² is preferably methyl, methoxymethyl, ethyl, allyl, cinnamyl, 2-propynyl, 2-butynyl, 2-pyridyl, optionally substituted phenyl, optionally substituted benzyl, optionally substituted 2-pyridylmethyl, optionally substituted 3-pyridylmethyl, optionally substituted 4-pyridylmethyl, optionally substituted 1-naphthyl, optionally substituted 2-naphthyl, optionally substituted 2-thenyl, optionally substituted 3-thenyl and the like. In the case R² is an optionally substituted benzyl, the substituent is not a group represented by formula:

wherein (R¹²)₂ is H₂, ═O, ═CH—OH, ═CHOCH₃, ═N—OH or ═N—OCH₃; and R¹³ represents an alkoxy or a monoalkylamino.

The alkoxy represented by R¹³ may be an alkoxy having 1 to 4 carbon atoms, and is typically methoxy, ethoxy, propoxy, butoxy and the like.

The monoalkylamino represented by R¹³ may be a monoalkylamino containing an alkyl having 1 to 4 carbon atoms, and is typically monomethylamino, monoethylamino and the like.

Examples of an optionally substituted alkyl represented by R³ may be those exemplified as an optionally substituted alkyl represented by R¹ described above.

Examples of an optionally substituted cycloalkyl represented by R³ may be those exemplified as an optionally substituted cycloalkyl represented by R¹ described above.

Examples of an optionally substituted alkenyl represented by R³ may be those exemplified as an optionally substituted alkenyl represented by R² described above.

Examples of an optionally substituted alkynyl represented by R³ may be those exemplified as an optionally substituted alkynyl represented by R² described above.

Examples of an optionally substituted alkylsulfonyl represented by R³ may be those exemplified as an optionally substituted alkylsulfonyl represented by R² described above.

Examples of an optionally substituted aryl represented by R³ may be those exemplified as an optionally substituted aryl represented by R¹ described above.

Examples of an optionally substituted arylsulfonyl represented by R³ may be those exemplified as an optionally substituted arylsulfonyl represented by R² described above.

Examples of an optionally substituted heterocyclic group represented by R³ may be those exemplified as an optionally substituted heterocyclic group represented by R² described above.

R³ is preferably methyl, ethyl, propyl, isopropyl, allyl, cinnamyl, 2-propynyl, 2-butynyl, 2-pyridyl, optionally substituted benzyl, optionally substituted 2-phenylethyl, optionally substituted 2-pyridylmethyl, optionally substituted 3-pyridylmethyl, optionally substituted 4-pyridylmethyl, optionally substituted benzenesulfonyl and the like.

Examples of an optionally substituted alkyl represented by each of R⁴ and R⁵ may be those exemplified as an optionally substituted alkyl represented by R¹ described above.

Examples of an optionally substituted cycloalkyl represented by each of R⁴ and R⁵ may be those exemplified as an optionally substituted cycloalkyl represented by R¹ described above.

Examples of the alkoxy in an optionally substituted alkoxy represented by each of R⁴ and R⁵ may for example be an alkoxy having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, and is typically, methoxy, ethoxy, propoxy, isopropoxy, butoxy and the like.

Examples of the substituent on an optionally substituted alkoxy represented by each of R⁴ and R⁵ may be similar to those exemplified as the substituent on a substituted alkyl represented by R¹ described above.

R⁴ and R⁵ may be the same or different from each other. Alternatively, R⁴ and R⁵ may be taken together to form an optionally substituted monocyclic ring or polycyclic ring. Such monocyclic ring or polycyclic ring means a 4- to 8-membered cyclic system formed together with the nitrogen atom to which the two substituents are bound and optionally containing a hetero atom (e.g., oxygen, nitrogen, sulfur and the like), as well as the polycyclic ring formed as a result of condensation of these rings with other rings. Examples of such monocyclic ring and polycyclic ring are pyrrolidine, piperidine, morpholine, thiomorpholine, piperazine, hexamethyleneimine, oxazolane, diazepane, tetrahydroquinoline, tetrahydroisoquinoline and the like. The substituent on each of these cyclic systems may be those exemplified as the substituent on an optionally substituted alkyl represented by R¹ described above, as well as an optionally substituted lower alkyl (e.g., methyl, ethyl, propyl, 2-chloroethyl, methoxymethyl, 2-ethoxyethyl, benzyl, 4-chlorobenzyl, 2-oxopropyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, carbamoylmethyl and the like), formyl, a lower alkanoyl (e.g., acetyl, propionyl and the like) and the like. Each of these substituents may be in any possible position on the respective cyclic system, and may occur one to four times.

The group —NR⁴R⁵ is preferably —NH₂, —NHMe, —NMe₂, —NEt₂, —N(Me)Et, —N(OMe)Me, optionally substituted 1-pyrrolidinyl, optionally substituted piperidino, optionally substituted morpholino, optionally substituted 4-thiomorpholinyl, optionally substituted 1-piperazinyl, optionally substituted 2-oxazolanyl, optionally substituted diazepan-1-yl.

Examples of an optionally substituted alkyl represented by R⁶ may be those exemplified as an optionally substituted alkyl represented by R¹ described above.

Examples of an optionally substituted aryl represented by R⁶ may be those exemplified as an optionally substituted aryl represented by R¹ described above.

The optionally substituted alkanoyl represented by R⁶ may be an optionally substituted alkanoyl having 2 to 6 carbon atoms, preferably 2 to 4 carbon atoms, and is typically acetyl, propionyl, trifluoroacetyl and the like.

The optionally substituted aroyl represented by R⁶ may be an optionally substituted aroyl having 7 to 16 carbon atoms, preferably 7 to 12 carbon atoms, and is typically benzoyl, 2-methylbenzoyl, 3-methylbenzoyl, 4-methylbenzoyl, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 4-methoxybenzoyl and the like.

Preferred examples of X are an oxygen atom, —NH—, —N(Me)—, —N(Ph)— and the like.

Preferred examples of Y are an oxygen atom, —NH—, —N(Me)—, —N(Et)—, —N(Ph)—, —N(Ac)—, —N(Bz)— and the like.

Examples of an alkyl represented by R⁷ may be those exemplified as an alkyl represented by R¹ described above.

R⁷ is preferably a hydrogen atom, methyl and ethyl.

While a compound according to the present invention occurs as any of the two isomers, i.e., an E form and a Z form, with respect to its imino moiety, the present invention encompasses these isomers as well as a mixture of these isomers in any ratio. Such isomerism is designated in the present invention using a wave-shaped line (˜) in a formula.

A compound according to the present invention may also form a salt in its amino group when its hydrazone moiety or its primary to tertiary amino group is substituted, and such salt may be a mineral acid salt (e.g., hydrochlorides, sulfates, nitrates and the like) as well as an organic acid salt (e.g., acetates, maleates and the like).

A compound according to the present invention may be in a form of a hydrate.

Compound (I) according to the present invention (i.e., a compound represented by Formula (I); Hereinafter the same abbreviation may apply analogously to a compound represented by another formula) and Compound (II) may for example be produced via a synthetic route shown below.

[Route 1]

wherein each radical is defined as described above.

Thus, a compound according to the present invention represented by Formula (Ia) can be prepared by reacting a hydroxylamine derivative or a hydrazine derivative represented by Formula (IV) or its salt (e.g., hydrochloride, sulfate) with Compound (III) in a suitable solvent (a single solvent or a solvent mixture).

When a salt is employed, the reaction may be performed after neutralization with a base. Examples of a base which may be employed are metal hydroxides (e.g., sodium hydroxide, potassium hydroxide and the like), metal carbonates (e.g., sodium carbonate, potassium carbonate and the like), metal acetates (sodium acetate, potassium acetate and the like), metal alkoxides (e.g., sodium methoxide, sodium ethoxide and the like), pyridine and the like, and the amount to be used is 1 to 3 equivalents, relative to a salt of Compound (IV), preferably 1 to 2 equivalents.

In this reaction, Compound (IV) can be used in an amount of 1 equivalent or more, relative to Compound (III), preferably 1 to 3 equivalents.

Examples of a solvent which can be employed are aromatic hydrocarbons (toluene, benzene, xylene and the like), saturated hydrocarbons (e.g., cyclohexane, hexane and the like), alcohols (e.g., methanol, ethanol, propanol and the like), ethers (e.g., tetrahydrofuran, dioxane and the like), acetic acid, water as well as a mixture thereof.

The reaction temperature may be 0 to 160° C., preferably 20 to 130° C. While the reaction time varies depending on reactants, a time of 0.5 to 90 hours may be sufficient.

A desired Compound (Ia) thus obtained may be purified by a standard method (e.g., column chromatography, recrystallization and the like).

Compound (III) employed as a starting material in this reaction may be prepared by a method described in Reference Example 1 discussed later in this specification or an analogous method.

A hydroxylamine derivative or a hydrazine derivative represented by Formula (IV) is known per se, or, may be prepared by a known method similar to that described in Methoden der Organischen Chemie, Vol.X/1 and X/2 by Houben-Weyl.

[Route 2]

wherein L represents a halogen atom (e.g., chlorine atom, bromine atom and the like), an alkylsulfonyloxy (e.g., methylsulfonyloxy, ethylsulfonyloxy and the like) or an arylsulfonyloxy which may be substituted by a halogen atom or a lower alkyl (e.g., benzensulfonyloxy, p-toluenesulfonyloxy, m-toluenesulfonyloxy, o-toluenesulfonyloxy and the like), and other radicals are defined as described above.

Thus, a compound according to the present invention represented by Formula (Ia′) can be prepared by reacting Compound (V) and Compound (VI) in the presence of a base in a suitable solvent (a single solvent or a solvent mixture).

In this reaction, Compound (VI) can be used in an amount of 1 equivalent or more, relative to Compound (V), preferably 1 to 2 equivalents.

Examples of a base which may be employed are metal hydroxides (e.g., sodium hydroxide, potassium hydroxide and the like), metal hydrides (e.g., sodium hydride, potassium hydride and the like), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium t-butoxide and the like), metal carbonates (e.g., sodium carbonate, potassium carbonate and the like) and the like, and the amount to be used is 1 equivalent or more, relative to Compound (V), preferably 1 to 2 equivalents.

Examples of a solvent which can be employed are N,N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), aromatic hydrocarbons (toluene, benzene, xylene and the like), saturated hydrocarbons (e.g., cyclohexane, hexane and the like), ethers (e.g., tetrahydrofuran, dioxane and the like), ketones (e.g., acetone, methylethylketone and the like), water as well as a mixture thereof.

The reaction temperature may be −30 to 150° C., preferably −10 to 100° C. While the reaction time varies depending on reactants, a time of 0.5 to 90 hours may be sufficient.

A desired Compound (Ia′) thus obtained may be purified by a standard method (e.g., column chromatography, recrystallization and the like).

Compound (V) employed as a starting material in this reaction may be prepared by a method described in WO 96/11183 or an analogous method.

[Route 3]

wherein R⁷′ represents an alkyl and other radicals are defined as described above.

Thus, a compound according to the present invention represented by Formula (Ia) can be prepared by reacting Compound (IIa) and Compound (VII) in the presence or absence of a suitable solvent (a single solvent or a solvent mixture).

In this reaction, Compound (VII) can be used in an amount of 1 equivalent or more, relative to Compound (IIa), preferably 1 to 30 equivalents.

Examples of a solvent which can be employed are hydrocarbons (e.g., benzene, toluene, xylene and the like), halogenated hydrocarbons (e.g., chloroform, 1,2-dichloroethane and the like), ethers (e.g., tetrahydrofuran, dioxane and the like), alcohols (e.g., methanol, ethanol, n-propanol, isopropanol and the like), N,N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), saturated hydrocarbons (e.g., cyclohexane, hexane and the like), nitrites (e.g., acetonitrile and the like), water as well as a mixture thereof.

The reaction temperature may be −30 to 160° C., preferably −10 to 120° C. While the reaction time varies depending on reactants, a time of 0.5 to 120 hours may be sufficient.

A desired Compound (Ia) thus obtained may be purified by a standard method (e.g., column chromatography, recrystallization and the like).

Compound (IIa) employed as a starting material in this reaction may be prepared via Route 4 and Route 5 shown below.

[Route 4]

wherein the radicals are defined as described above.

Thus, a compound represented by Formula (IIa) can be prepared by reacting Compound (VII) and Compound (IV) in a suitable solvent (a single solvent or a solvent mixture) similarly as in Scheme 1 described above.

A desired Compound (IIa) thus obtained may be purified by a standard method (e.g., column chromatography, recrystallization and the like).

Compound (VIII) employed as a starting material in this reaction may be prepared by a method described in Reference Example 2 discussed later in this specification or an analogous method.

[Route 5]

wherein the radicals are defined as described above.

Thus, a compound represented by Formula ((IIa′) can be prepared by reacting Compound (IX) and Compound (VI) in the presence of a base in a suitable solvent (a single solvent or a solvent mixture) similarly as in Scheme 2 described above.

A desired Compound (IIa′) thus obtained may be purified by a standard method (e.g., column chromatography, recrystallization and the like).

Compound (IX) employed as a starting material in this reaction may be prepared by a method described in WO96/11183 or an analogous method.

[Route 6]

wherein the radicals are defined as described above.

Thus, a compound represented by Formula (IIb) can be prepared by reacting an acid or a base with Compound (IIa) in a suitable solvent.

Example of an acid which may be employed are hydrochloric acid, hydrobromic acid, trifluoroacetic acid, p-toluenesulfonic acid and the like, and each may be used in an amount of 0.1 equivalent or more, relative to Compound (IIa), preferably 0.1 to 3 equivalents.

Examples of a base which may be employed are sodium hydroxide, potassium hydroxide, and the like, and each may be used in an amount of 1 equivalent or more, preferably 1 to 3 equivalents.

Examples of a solvent which can be employed are hydrocarbons (e.g., benzene, toluene, xylene and the like), halogenated hydrocarbons (e.g., chloroform, 1,2-dichloroethane and the like), ethers (e.g., tetrahydrofuran, dioxane and the like), alcohols (e.g., methanol, ethanol, n-propanol, isopropanol and the like), water as well as a mixture thereof.

The reaction temperature may be 0 to 150° C., preferably 20 to 100° C. The reaction time is generally 15 minutes to 100 hours.

A desired Compound (IIb) thus obtained may be purified by a standard method (e.g., column chromatography, recrystallization and the like).

A compound represented by Formula (II):

wherein the radicals are defined as described above, consisting of Compound (IIa) and Compound (IIb) obtained in Scheme 4, Scheme 5 and Scheme 6 described above, is a novel compound, and encompassed in the present invention.

wherein the radicals are defined as described above.

Thus, a compound represented by Formula (Ia) can be prepared by reacting Compound (IIb) and Compound (VII) in the presence of a suitable condensing agent in a suitable solvent (a single solvent or a solvent mixture).

In this reaction, Compound (VII) may be used in an amount of 1 equivalent or more, relative to Compound (IIb), preferably 1 to 5 equivalents.

Examples of a condensing agent are N,N′-dicyclohexylcarbodiimide, 1,1′-carbonyldiimidazole, diphenylphosphoric acid azide, diethylphosphoric acid cyanide, ethyl chlorocarbonate, isopropyl chlorocarbonate and the like, and each may be used in an amount of 1 equivalent or more, relative to Compound (IIb) preferably 1 to 3 equivalents.

An organic base such as triethylamine, diisopropylethylamine, pyridine and the like, or an inorganic base such as sodium hydroxide, potassium hydroxide may be used in an amount of 1 to 5 equivalents or more, relative to Compound (IIb), preferably 1 to 2 equivalents.

Examples of a solvent which can be employed are hydrocarbons (e.g., benzene, toluene, xylene and the like), halogenated hydrocarbons (e.g., chloroform, 1,2-dichloroethane and the like), ethers (e.g., tetrahydrofuran, dioxane and the like), alcohols (e.g., methanol, ethanol, n-propanol, isopropanol and the like), N,N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), saturated hydrocarbons (e.g., cyclohexane, hexane and the like), nitrites (e.g., acetonitrile and the like) as well as a mixture thereof.

The reaction temperature may be −30 to 100° C., preferably −20 to 80° C. While the reaction time varies depending on reactants, a time of 0.5 to 120 hours may be sufficient.

A desired Compound (Ia) thus obtained may be purified by a standard method (e.g., column chromatography, recrystallization and the like).

[Route 7]

wherein the radicals are defined as described above.

Thus, a compound represented by Formula (X) can be prepared by chlorinating Compound (IIb) in a suitable solvent (a single solvent or a solvent mixture).

Examples of a chlorinating agent are thionyl chloride, oxalyl chloride, phosphorus oxychloride, phosphorus pentachloride, carbon tetrachloride-triphenylphosphine and the like, and each may be used in an amount of 1 to 5 equivalents, relative to Compound (IIb), preferably 1 to 2 equivalents.

A small amount of N,N-dimethylformamide (DMF) may be used as a reaction catalyst.

Examples of a solvent which can be employed are hydrocarbons (e.g., benzene, toluene, xylene and the like), halogenated hydrocarbons (e.g., chloroform, 1,2-dichloroethane and the like), ethers (e.g., tetrahydrofuran, dioxane and the like), nitrites (e.g., acetonitrile and the like) as well as a mixture thereof.

The reaction temperature may be −20 to 120° C., preferably 0 to 100° C. While the reaction time varies depending on reactants, a time of 0.5 to 60 hours may be sufficient.

A desired Compound (X) thus obtained may be used in the subsequent step as a reaction solution or a crude product, or after being purified by a standard method (e.g., distillation, crystallization and the like).

wherein the radicals are defined as described above.

Thus, a compound represented by Formula (Ia) can be prepared by reacting Compound (X) and Compound (VII) in a suitable solvent (a single solvent or a solvent mixture).

In this reaction, Compound (VII) may be used in an amount of 1 equivalent or more, relative to Compound (X), preferably 1 to 5 equivalents.

An organic base such as triethylamine, diisopropylethylamine, pyridine and the like, or an inorganic base such as sodium hydroxide, potassium hydroxide may be used in an amount of 1 to 5 equivalents or more, relative to Compound (X), preferably 1 to 2 equivalents.

Examples of a solvent which can be employed are hydrocarbons (e.g., benzene, toluene, xylene and the like), halogenated hydrocarbons (e.g., chloroform, 1,2-dichloroethane and the like), ethers (e.g., tetrahydrofuran, dioxane and the like), nitrites (e.g., acetonitrile and the like), water as well as a mixture thereof.

The reaction temperature may be −30 to 100° C., preferably −10 to 80° C. While the reaction time varies depending on reactants, a time of 0.5 to 24 hours may be sufficient.

A desired Compound (Ia) thus obtained may be purified by a standard method (e.g., column chromatography, recrystallization and the like).

[Route 8]

wherein the radicals are defined as described above.

Thus, a compound represented by Formula (XII) can be prepared by reacting Compound (IV) with Compound (XI) in a suitable solvent (a single solvent or a solvent mixture) similarly as in Scheme 1 described above.

A desired Compound (XII) thus obtained may be used in the subsequent step, as a reaction solution or a crude product, or after being purified by a standard method (e.g., distillation, crystallization and the like).

Compound (XI) employed as a starting material in this reaction is known per se, or may be prepared by a known method similar to that described in Synthesis, page 290 (1993).

wherein the radicals are defined as described above.

Thus, a compound represented by Formula (XIII) can be prepared by reacting Compound (XII) with selenium dioxide in a suitable solvent (a single solvent or a solvent mixture).

In this reaction, selenium dioxide may be used in an amount of 1 equivalent or more, relative to Compound (XII), preferably 1 to 3 equivalents.

Examples of a solvent which can be employed are aromatic hydrocarbons (toluene, benzene, xylene and the like), halogenated aromatic hydrocarbons (e.g., chlorobenzene, dichlorobenzene and the like), saturated hydrocarbons (e.g., cyclohexane, hexane and the like), alcohols (e.g., methanol, ethanol, propanol and the like), ethers (e.g., tetrahydrofuran, dioxane and the like), acetic acid, water as well as a mixture thereof.

The reaction temperature may be 30 to 180° C., preferably 50 to 160° C. While the reaction time varies depending on reactants, a time of 0.5 to 50 hours may be sufficient.

A desired Compound (XIII) thus obtained may be used in the subsequent step, as a reaction solution or a crude product, or after being purified by a standard method (e.g., distillation, crystallization and the like).

wherein the radicals are defined as described above.

Thus, a compound represented by Formula (XIV) can be prepared by reacting Compound (XIII) and Compound (VII) in the presence or absence of a suitable solvent (a single solvent or a solvent mixture) similarly as in Scheme 3 described above.

A desired Compound (XIV) thus obtained may be used in the subsequent step, as a reaction solution or a crude product, or after being purified by a standard method (e.g., distillation, crystallization and the like).

wherein the radicals are defined as described above.

Thus, a compound represented by Formula (Ib) can be prepared by reacting a hydroxylamine derivative or a hydrazine derivative represented by Formula (XV) or its salt (e.g., hydrochloride, sulfate) and Compound (XIV) in a suitable solvent (a single solvent or a solvent mixture) similarly as in Scheme 1 described above.

A desired Compound (Ib) thus obtained may be purified by a standard method (e.g., column chromatography, recrystallization and the like).

A hydroxylamine derivative or a hydrazine derivative represented by Formula (XV) is known per se, or, may be prepared by a known method similar to that described in Methoden der Organischen Chemie, Vol.X/1 and X/2 by Houben-Weyl.

[Route 9]

wherein the radicals are defined as described above.

Thus, a compound represented by Formula (Ic) can be prepared by reacting Compound (Ib′) and Compound (XVI) in the presence of a base in a suitable solvent (a single solvent or a solvent mixture).

In this reaction, Compound (XVI) may be used in an amount of 1 equivalent or more, relative to Compound (Ib′), preferably 1 to 10 equivalents.

Examples of a base which may be employed are metal hydroxides (e.g., sodium hydroxide, potassium hydroxide and the like), metal hydrides (e.g., sodium hydride, potassium hydride and the like), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium t-butoxide and the like), metal carbonates (e.g., sodium carbonate, potassium carbonate and the like), pyridine, triethylamine and the like, and the amount to be used is 1 equivalent or more, relative to Compound (Ib′), preferably 1 to 20 equivalents.

Examples of a solvent which can be employed are N,N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), aromatic hydrocarbons (toluene, benzene, xylene and the like), saturated hydrocarbons (e.g., cyclohexane, hexane and the like), ethers (e.g., tetrahydrofuran, dioxane and the like), ketones (e.g., acetone, methylethylketone and the like), water as well as a mixture thereof.

The reaction temperature may be −30 to 150° C., preferably −10 to 100° C. While the reaction time varies depending on reactants, a time of 0.1 to 90 hours may be sufficient.

A desired Compound (Ic) thus obtained may be purified by a standard method (e.g., column chromatography, recrystallization and the like).

[Route 10]

wherein the radicals are defined as described above.

Thus, a compound represented by Formula (Id) can be prepared by reacting Compound (lb) with a sulfurizing agent in a suitable solvent (a single solvent or a solvent mixture).

As a sulfurizing agent, phosphorus pentasulfide or Lawson's reagent may be mentioned, and each is used in an amount of 1 to 5 equivalents, relative to Compound (Ib), preferably 1 to 2 equivalents.

Examples of a solvent which can be employed are hydrocarbons (benzene toluene, xylene and the like), pyridine as well as a mixture thereof.

The reaction temperature may be 10 to 200° C., preferably 60 to 150° C. While the reaction time varies depending on reactants, a time of 0.5 to 48 hours may be sufficient.

A desired Compound (Id) thus obtained may be purified by a standard method (e.g., column chromatography, recrystallization and the like).

Compound (I) according to the present invention or its salt or hydrate is effective against pathogenic microbes (fungi) and soil fungi on crop plants or their seeds such as rice, wheat, barley, rye, corn, millet, foxtail millet, buckwheat, soybean, redbean, peanut, and the like, fruit trees such as citrus fruits, grape, apple, pear, peach and the like, or vegetables such as cucumber, eggplant, tomato, pumpkin, kidney bean and the like. The compound of this invention shows a potent fungicidal activity particularly against a rice blight microorganism (Pyricularia oryzae), a sheath blight microorganism (Rhizoctonia solani), a wheat powdery mildew microorganism (Erysiphe graminis), a cucumber mildew microorganism (Sphaerotheca fuliginea), a tobacco mildew microorganism (Erysiphe cichoracearum), a potato late blight microorganism (Phylophthora infestans), a cucumber downy mildew microorganism (Pseudoperonospora cubensis), a soybean downey mildew microorganism (Peronospora manshurica), a grape downy mildew microorganism (Plasaopara viticola), a grey mold microorganism (Botrytis cinerea) of vegetables, grape and the like, a cucumber seedle damping off microorganism (Pythium aphanidermatum), a sclerotium disease microorganism (Sclerotinia sclerotiorum) of buckwheat, soybean, rape and the like, a stem rot microrganism (Corticium rolfsii) of soybean, red bean, potato, peanut and the like, a wheat eyespot disease microorganism (Pseudocercosporella herpotrichoides) and the like. Therefore, Compound (I) according to the present invention or its salt or hydrate is useful as a fungicide, particularly as an agricultural fungicide.

Application of Compound (I) according to the present invention or a salt or a hydrate thereof as agrochemicals may be to a plant may be performed by any conventional procedure such as atomizing, scattering or spreading of an active compound, or, alternatively, the application may be performed by mans of a treatment of a seed of a plant, a soil where a plant grows, a soil for seeding, a paddy field or a water for perfusion with an active compound. Application may be performed before or after an infection with a phytopathogenic microorganism.

A compound according to the present invention can be used as an agrochemical formulation suitable for an agricultural fungicide, such as a solution, a wettable powder, an emulsion, a suspension, a concentrated liquid preparation, a tablet, a granule, an aerosol, a powder, a paste, a fumigant and the like.

Such formulation can be prepared in a conventional manner by mixing at least one compound according to the present invention with an appropriate solid or liquid carrier and, if necessary, an appropriate adjuvant (e.g., surfactant, spreader, dispersant, stabilizer and the like) for improving the dispersibility and other properties of an active ingredient.

Examples of a solid carrier or a diluent are a botanical material (e.g., flour, tobacco stalk powder, soybean powder, walnut-shell powder, vegetable powder, saw dust, bran, bark powder, cellulose powder, vegetable extract residue and the like), a fibrous material (e.g., paper, corrugated cardboard, old rag and the like), an artificial plastic powder, a clay (e.g., kaolin, bentonite, fuller's earth and the like), talc, other inorganic materials (e.g., pyrophyllite, sericite, pumice, sulfur powder, activated carbon and the like), a chemical fertilizer (e.g., ammonium sulfate, ammonium phosphate, ammonium nitrate, urea, ammonium chloride and the like) and the like.

Examples of a liquid carrier or a diluent are water, alcohols (e.g., methanol, ethanol and the like), ketones (e.g., acetone, methyl ethyl ketone and the like), ethers (e.g., diethylether, dioxane, cellosolve, tetrahydrofuran), aromatic hydrocarbons (e.g., benzene, toluene, xylene, methylnahthalene and the like), aliphatic hydrocarbons (e.g., gasoline, kerosene, lamp oil and the like), esters, nitriles, acid amides (e.g. dimethylformamide, dimethylacetamide and the like), halogenated hydrocarbons (e.g., dichloroethane, carbon tetrachloride and the like) and the like.

Examples of a surfactant are an alkyl sulfuric, an alkyl ester, an alkylaryl sulfuric ester, a polyethylene glycol ether, a polyhydric alcohol ester and the like. Examples of a spreader or a dispersant are casein, gelatin, starch powder, carboxymethylcellulose, gum arabic, alginic acid, lignin, bentonite, molasses, polyvinyl alcohol, pine oil, agar and the like. Examples of a stabilizer are PAP (a mixture of isopropylphosphate), tricresyl phosphate (TCP), tall oil, an epoxidized oil, a surfactant, a fatty acid and its ester and the like.

A composition according to the present invention may contain other fungicides, insecticides, herbicides or fertilizers in addition to the ingredients listed above.

In general, a composition described above contains at least one compound of Formula (I) of the present invention or its salt or hydrate in a concentration of 0.1 to 95% by weight, preferably 1.0 to 80% by weight. The composition can be used as it is or in a diluted form, and about 1.0 g to 5 kg/ha, preferably about 10 g to 1.0 kg/ha, of a compound according to the present invention is used in a concentration of normally about 1 to 5,000 ppm, preferably about 10 to 1,000 ppm.

A compound of Formula (I) according to the present invention or its salt or hydrate is useful as a prophylactic or therapeutic agent in mammals including human against tachykinin receptor antagonism-related inflammatory diseases, gastrointestinal diseases, vomiting, dysuria, pain, migraine, neuralgia, Alzheimer's disease, immunopotentiation or immunosuppression-related diseases, rheumatoid diseases, allergic diseases and the like.

A compound of Formula (I) according to the present invention or its salt or hydrate may be administered as a pharmaceutical via any route such as oral, topical and parenteral routes.

A compound according to the present invention may be used as a pharmaceutical formulation for a medical use such as a powder, a fine granule, a granule, a tablet, a capsule, a solution for injection and the like.

Such formulation may be obtained by an ordinary process in which at least one of the compounds according to the present invention is mixed with a suitable solid or liquid carrier, and, if desired, an excipient (e.g., starch, lactose, sugar, potassium carbonate, calcium phosphate and the like), a binder (e.g., starch, gum arabic, carboxymethylcellulose, hydroxypropylcellulose, crystalline cellulose, alginic acid, gelatin, polyvinylpyrrolidone and the like), a glidant (e.g., stearic acid, magnesium stearate, calcium stearate, talc and the like), a disintegrant (e.g., potassium carboxymethylcellulose, talc and the like), a diluent (e.g., physiological saline and the like).

In general, a pharmaceutical described above may be given in a dose which may vary depending on the administration route as well as the symptoms and the ages of the subjects, and the daily dose, as at least one Compound (I) according to the present invention or its salt or hydrate, may be about 0.001 mg to 50 mg, preferably about 0.01 mg to 10 mg, per kg body weight, which may be given as being divided to 3 dosages or less a day.

EXAMPLES

The following Examples and Test Examples further illustrate the present invention in detail, but are not to be construed to limit the scope thereof The ¹H-NMR (CDCl₃) data in Examples and Tables shown later were determined at 270 MHz in CDCl₃ using tetramethylsilane as an internal standard and indicated in δ values (ppm). The coupling constants (J) are indicated in Hz. In the data, s is a singlet, d is a doublet, t is a triplet, q is a quartet, AB is a ABq type quartet, sept is a septet and m is a multiplet.

Reference Example 1

Synthesis of 2-methoxyimino-N,N-dimethylacetoacetamide

18.04 g (0.2 mol) of a 50% aqueous solution of dimethylamine in 10 ml toluene was cooled in an ice bath and combined with 8.41 g (0.1 mol) of a diketene in 20 ml of toluene and stirred for 1 hour at room temperature. After distilling water off azeotropically, 200 ml of ethyl acetate was added and the mixture was dried over with anhydrous sodium sulfate to distill the solvent off. To the residue thus obtained, 7.63 g (0.105 mol) of sodium nitrite was added and the mixture was cooled in an ice bath and then 10 ml (0.12 mol) of a concentrated hydrochloric acid was added dropwise. After stirring for 0.5 hour at room temperature, the reaction mixture was cooled again in an ice bath, and 5.42 g (0.13 mol) of sodium hydroxide was added. The solution thus obtained was added to a solution of 18.92 g (0.15 mol) of dimethyl sulfate and 1.61 g (0.05 mol) of tetrabutylammonium bromide in 50 ml of toluene dropwise while cooling with an ice, and the mixture was stirred for 4 hours at room temperature. The reaction mixture was extracted four times with 150 ml of ethyl acetate and dried over with anhydrous magnesium sulfate, and then the solvent was distilled off, and finally the residue thus obtained was purified by a column chromatography on a silica gel (n-hexane/ethyl acetate) to obtain 13.46 g (yield: 78%) of 2-methoxyimino-N,N-dimethylacetoacetamide as a colorless crystal.

(Melting point: 73.5 to 75° C.)

Example 1

Synthesis of 2-methoxyimino-N,N-dimethyl-3-(N-methyl-N-phenylhydrazono)butyramide (Compound No.1-1)

1.0 g (5.8 mmol) of 2-methoxyimino-N,N-dimethylacetoacetamide was dissolved in 15 ml of ethanol and 0.5 ml of acetic acid, and 0.78 g (6.4 mmol) of N-methyl-N-phenylhydrazine was added and the mixture was stirred for 24 hours at room temperature. After distilling the solvent off, water was added and the mixture was extracted three times with 20 ml of diethylether. After washing with a dilute hydrochloric acid, water and a saturated aqueous sodium chloride, the mixture was dried over with anhydrous magnesium sulfate, and the solvent was distilled off, and finally the residue thus obtained was purified by a column chromatography on a silica gel (n-hexane/ethyl acetate) to obtain 1.38 g (yield: 86%) of 2-methoxyimino-N,N-dimethy-3-(N-methyl-N-phenylhydrazono)butyramide as a yellow oil. ¹H-NMR(CDCl₃) δ ppm:2.13(3H, s), 2.90(3H,s), 3.07(3H, s), 3.29(3H, s), 3.99(3H,s), 6.90-7.02(3H, m), 7.33-7.29(2H, m).

Example 2

Synthesis of 3-(4-methylbenzyloxyimino)-2-methoxyimino-N,N-dimethylbutyramide (Compound No.C-376)

To a solution of 600 mg (3.2 mmol) of 3-hydroxyimino-2-methoxyimino-N,N-dimethylbutyramide in 20 ml of acetone, 500 mg (3.5 mmol) of 4-methylbenzylchloride and 660 mg (4.8 mmol) of potassium carbonate were added and the mixture was heated under reflux for 16 hours. The reaction mixture was combined with 30 ml of water and extracted three times with 30 ml of diethylether. After washing with water and a saturated aqueous sodium chloride, the mixture was dried over with anhydrous magnesium sulfate and then the solvent was distilled off. The residue thus obtained was purified by a column chromatography on a silica gel (n-hexane/ethyl acetate) to obtain 900 mg (yield: 96%) of 3-(4-methylbenzyloxyimino)-2-methoxyimino-N,N-dimethylbutyramide as a colorless crystal.

(Melting point: 68 to 69° C.)

Reference Example 2

Synthesis of methyl 2-benzyloxyiminoacetoacetate

(1) Synthesis of methyl 2-hydroxyiminoacetoacetate

To a solution of 46.45 g (0.4 mol) of methyl acetoacetate in 200 ml of diethylether, 30.4 g (0.44 mol) of sodium nitrite was added and the mixture was cooled in an ice bath and treated dropwise with 40 ml (0.48 mol) of a concentrated hydrochloric acid. After stirring for 1 hour at room temperature, 200 ml of water was added and the mixture was extracted three times with 200 ml of diethylether. After washing with water and a saturated aqueous sodium chloride followed by drying over with anhydrous magnesium sulfate, the solvent was distilled off to obtain 50.09 g (yield: 86%) of a crude methyl 2-hydroxyiminoacetoacetate as a pale yellow oil. (2) Synthesis of methyl 2-benzyloxyiminoacetoacetate

To a solution of 15.0 g (103 mmol) of methyl 2-hydroxyiminoacetoacetate in 200 ml of acetone, 14.4 g (113 mmol) of benzyl chloride and 21.4 g (155 mmol) of potassium carbonate were added and the mixture was heated under reflux for 15 hours. The reaction mixture was combined with 200 ml of water and extracted three times with 200 ml of diethylether. After washing with water and a saturated aqueous sodium chloride followed by drying over with anhydrous magnesium sulfate, the solvent was distilled off. The residue thus obtained was purified by a column chromatography on a silica gel (n-hexane/ethyl acetate) to obtain 18.7 g (yield: 77%) of methyl 2-benzyloxyiminoacetoacetate as a colorless crystal.

(Melting point: 35 to 36° C.)

Example 3

Synthesis of methyl 2-benzyloxyimino-3-methoxyiminobutyrate (Compound No.x-10)

To a solution of 4.0 g (17 mol) of methyl 2-benzyloxyiminoacetoacetate in 50 ml of methanol, 1.56 g (18.7 mmol) of methoxyamine hydrochloride was added and the mixture was heated under reflux for 3 hours. After distilling the solvent off under reduced pressure, 50 ml of water was added and the mixture was extracted twice with 50 ml of diethylether and then washed with water and a saturated aqueous sodium chloride. The organic layer was dried over with anhydrous magnesium sulfate and the solvent was distilled off to obtain a residue, which was then purified by a column chromatography on a silica gel (n-hexane/ethyl acetate) to obtain 4.11 g (yield:91%) of methyl 2-benzyloxyimino-3-methoxyiminobutyrate as a colorless oil. ¹H-NMR(CDCl₃) δ ppm:1.99(3H, s), 3.86(3H, s), 3.94(3H, s), 5.21(2H, s), 7.33(5H, m).

Example 4

Synthesis of 2-benzyloxyimino-3-methoxyiminobutyric acid (Compound No. z-10)

To a solution of 3.2 g (12.1 mmol) of methyl 2-benzyloxyimino-3-methoxyiminobutyrate in 50 ml of methanol, 1.01 g (24.2 mmol) of sodium hydroxide and 10 ml of water were added and the mixture was heated under reflux for 24 hours. After distilling the solvent off under reduced pressure and adding 50 ml of water, the mixture was washed with 50 ml of diethylether. The aqueous layer was made acidic by adding a concentrated hydrochloric acid, and then the mixture was extracted three times with 50 ml of diethylether. After washing with water and with a saturated aqueous sodium chloride, the organic layer was dried over with anhydrous magnesium sulfate and the solvent was distilled off to obtain 3.02 g (yield: 100% ) of 2-benzyloxyimino-3-methoxyiminobutyric acid as a white solid.

(Melting point: 88 to 89° C.)

Example 5

Synthesis of 2-benzyoxyimino-3-methoxyimino-N,N-dimethylbutyramide (Compound No.C-10)

To a solution of 0.9 g (3.6 mmol) of 2-benzyloxyimino-3-methoxyiminobutyric acid in 15 ml of toluene, 0.5 g (4.0 mmol) of thionyl chloride and one drop of N,N-dimethylformamide were added and the mixture was stirred for 1 hour at 60° C. After cooling with an ice, 5 ml of 50% dimethylamine solution was added and the mixture was stirred for 0.5 hour at room temperature. 30 ml of water was added and the mixture was extracted three times with 50 ml of diethylether. After washing with water and a saturated aqueous sodium chloride, the organic layer was dried over with anhydrous magnesium sulfate and the solvent was distilled off to obtain a residue, which was then purified by a column chromatography on a silica gel (n-hexane/ethyl acetate) to obtain 0.53 g (yield: 53%) of 2-benzyloxyimino-3-methoxyimino-N,N-dimethylbutyramide as a colorless oil.

¹H-NMR(CDCl₃) δ ppm:2.02(3H, s), 2.74(3H, s), 3.00(3H, s), 3.92(3H, s), 5.19(2H, s), 7.33(5H,m).

Example 6

Synthesis of 4-(3-benzyloxyimino-2-(4-methoxybenzylhydrazono)valeryl)morpholine (Compound No. n-794)

(1) Synthesis of methyl 3-benzyloxyiminovalerate

To a solution of 26.03 g (0.2 mol) of methyl propionylacetate in 300 ml of methanol, 100 ml of water and 35.12 g (0.22 mol) of benzyloxyamine hydrochloride, 19.69 g (0.24 mol) of potassium acetate were added and the mixture was stirred for 15 hours at room temperature. After distilling methanol off under reduced pressure, followed by adding 200 ml of water and extracting three times with 200 ml of ethyl acetate, the mixture was washed with water and a saturated aqueous sodium chloride and then dried over with anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 47.06 g (yield: 100%) of a crude methyl 3-benzyloxyiminovalerate as a colorless oil.

(2) Synthesis of methyl 3-benzyloxyimino-2-oxovalerate.

To a solution of 47.06 g (0.2 mol) of methyl 3-benzyloxyiminovalerate in 150 ml of chlorbenzene, 24.41 g (0.22 mol) of selenium dioxide was added and the mixture was stirred for 8 hours at 120° C. After adding 200 ml of water and filtering through Celite, the filtrate was extracted three times with 200 ml of diethylether. After washing with water and a saturated aqueous sodium chloride followed by drying over with anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to obtain a residue, which was purified by a column chromatography on a silica gel (n-hexane/ethyl acetate) to obtain 31.15 g (yield 62%) of methyl 3-benzyloxyimino-2-oxovalerate as a colorless oil.

¹H-NMR(CDCl₃) δ ppm:1.04(3H, t, J=7.6), 2.52(2H, d, J=7.6), 3.86(3H, s), 5.29(2H, s), 7.36(5H, m).

(3) Synthesis of 4-(3-benzyloxyimino-2-oxyvaleryl)morpholine

10.0 g (0.04 mol) of methyl 3-benzyloxyimino-2-oxovalerate and 20 ml of morpholine were combined and the mixture was stirred for 3 hours at 100° C. After distilling the morpholine off under reduced pressure, 100 ml of water was added and the mixture was extracted three times with 100 ml of diethylether. After washing with water and a saturated aqueous sodium chloride followed by anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to obtain a residue, which was purified by a column chromatography on a silica gel (n-hexane/ethyl acetate) to obtain 6.78 g (yield: 56%) of 4-(3-benzyloxyimino-2-oxovaleryl)morpholine as a white solid.

¹H-NMR(CDCl₃) δ ppm:1.07(3H, t, J=7.6), 2.56(2H, q, J=7.6), 3.01(2H, t, J=4.9), 3.39(2H,t, J=4.9), 3.60-3.70(4H, m), 5.29(2H, s), 7.36(5H, m).

(4) Synthesis of 4-(3-benzyloxyimino-2-(4-methoxybenzylhydrazono)valeryl)morpholine

1.0 g (3.3 mmol) of 4-(3-benzyloxyimino-2-oxovaleryl)morpholine was dissolved in 20 ml of 2-propanol and 1.24 g (6.6 mmol) of 4-methoxybenzylhydrazine hydrochloride, 1.08 g (13.2 mmol) of sodium acetate and 1 ml of acetic acid were added and the mixture was refluxed for 15 hours. After distilling the solvent off under reduced pressure, 20 ml of water was added and the mixture was extracted three times with 30 ml of diethylether. After washing with 1N aqueous hydrochloric acid, water, a saturated aqueous sodium bicarbonate, water and then a saturated aqueous sodium chloride followed by drying over with anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to obtain a residue, which was purified by a column chromatography on a silica gel (n-hexane/ethyl acetate) to obtain 1.19 g (yield: 83%) of 4-(3-benzyloxyimino-2-(4-methoxybenzylhydrazono)valeryl)morpholine as a yellow oil.

¹H-NMR(CDCl₃) δ ppm: 1.08(3H, t, J=7.6), 2.63(2H, q, J=7.6), 2.94(2H, t, J=4.9), 3.29(2H,t, J=4.9), 3.59(4H, brs), 3.79(3H, s), 4.38(2H, d, J=4.9), 5.10(2H, s), 6.15(1H, t, J=4.9), 6.84(2H, d, J=8.5), 7.19(2H, d, J=8.5), 7.32(5H, m).

Example 7

Synthesis of 4-(3-benzyloxyimino-2-((4-methoxybenzyl)methylhydrazono)valeryl)morpholine (Compound No. o-794)

0.04 g (1.0 mmol) of 60% sodium hydride was suspended in 10 ml of N,N-dimethylformamide, and to this a solution of 0.40 g (0.91 mmol) of 4-(3-benzyloxyimino-2-(4-methoxybenzylhydrazono)valeryl)morpholine in 5 ml of N,N-dimethylformamide and 0.19 g (0.13 mmol) of methyl iodide were added and the mixture was stirred for 1 hour at room temperature. 20 ml of water was added and the mixture was extracted three times with 20 ml of diethylether. After washing with water and a saturated aqueous sodium chloride followed by drying over with anhydrous magnesium sulfate, the solvent was distilled off to obtain a residue, which was purified by a column chromatography on a silica gel (n-hexane/ethyl acetate) to obtain 0.35 g (yield: 85%) of 4-(3-benzyloxyimino-2-((4-methoxybenzyl)methylhydrazono)valeryl) as a yellow oil.

¹H-NMR(CDCl₃) δ ppm:1.07(3H, t, J=7.6), 2.65(2H, q, J=7.6), 2.84(3H, s), 2.92-2.98(2H, m), 3.23-3.69(6H, m), 3.79(3H, s), 4.32(1H, d, J=14.3), 4.36(1H, d, J=14.3), 5.05(1H, d, J=12.5), 5.15(1H, d, J=12.5), 6.84(2H, d, J=8.5), 7.18(2H, d, J=8.5), 7.33(5H, m).

Examples of the compounds represented by Formula (I) and (II) obtainable by the same manner as that in Examples described above are the following compound group A to Z, and a to w and x to z, and examples of combination of the substituents R¹, R² and R³ of the compound groups A to Z and a to z are shown in Tables 1 to 70. The physical data of the compounds are shown in Tables 71 to 83. The physical data of the compound obtained in the above Examples are also listed in the Tables. “No.” in each Table represents a compound number, and, for example, “A-176” means a compound which is included in compound group A and which has the combination of the substituent designated by No. 176.

TABLE 1 No R¹ R² R³ 1 Me Me Me 2 Me Me Et 3 Me Me n-Pr 4 Me Me i-Pr 5 Me Me allyl 6 Me Me cinnamyl 7 Me Me 2-propynyl 8 Me Me 2-butynyl 9 Me Me 2-pyridyl 10 Me Me benzyl 11 Me Me 2-Cl-benzyl 12 Me Me 3-Cl-benzyl 13 Me Me 4-Cl-benzyl 14 Me Me 2-Me-benzyl 15 Me Me 3-Me-benzyl 16 Me Me 4-Me-benzyl 17 Me Me 2-MeO-benzyl 18 Me Me 3-MeO-benzyl 19 Me Me 4-MeO-benzyl 20 Me Me 2-Cl-4-MeO-benzyl 21 Me Me 3,4-(Cl)₂-benzyl 22 Me Me 2-Me-4-MeO-benzyl 23 Me Me α-Me-4-MeO-benzyl 24 Me Me 4-MeO-PhSO₂ 25 Me Me 4-pyridylCH₂

TABLE 2 No R¹ R² R³ 26 Me MeOCH₂ Me 27 Me MeOCH₂ Et 28 Me MeOCH₂ n-Pr 29 Me MeOCH₂ i-Pr 30 Me MeOCH₂ allyl 31 Me MeOCH₂ cinnamyl 32 Me MeOCH₂ 2-propynyl 33 Me MeOCH₂ 2-butynyl 34 Me MeOCH₂ 2-pyridyl 35 Me MeOCH₂ benzyl 36 Me MeOCH₂ 2-Cl-benzyl 37 Me MeOCH₂ 3-Cl-benzyl 38 Me MeOCH₂ 4-Cl-benzyl 39 Me MeOCH₂ 2-Me-benzyl 40 Me MeOCH₂ 3-Me-benzyl 41 Me MeOCH₂ 4-Me-benzyl 42 Me MeOCH₂ 2-MeO-benzyl 43 Me MeOCH₂ 3-MeO-benzyl 44 Me MeOCH₂ 4-MeO-benzyl 45 Me MeOCH₂ 2-Cl-4-MeO-benzyl 46 Me MeOCH₂ 3,4-(Cl)₂-benzyl 47 Me MeOCH₂ 2-Me-4-MeO-benzyl 48 Me MeOCH₂ α-Me-4-MeO-benzyl 49 Me MeOCH₂ 4-MeO-PhSO₂ 50 Me MeOCH₂ 4-pyridylCH₂

TABLE 3 No R¹ R² R³ 51 Me Et Me 52 Me Et Et 53 Me Et n-Pr 54 Me Et i-Pr 55 Me Et allyl 56 Me Et cinnamyl 57 Me Et 2-propynyl 58 Me Et 2-butynyl 59 Me Et 2-pyridyl 60 Me Et benzyl 61 Me Et 2-Cl-benzyl 62 Me Et 3-Cl-benzyl 63 Me Et 4-Cl-benzyl 64 Me Et 2-Me-benzyl 65 Me Et 3-Me-benzyl 66 Me Et 4-Me-benzyl 67 Me Et 2-MeO-benzyl 68 Me Et 3-MeO-benzyl 69 Me Et 4-MeO-benzyl 70 Me Et 2-Cl-4-MeO-benzyl 71 Me Et 3,4-(Cl)₂-benzyl 72 Me Et 2-Me-4-MeO-benzyl 73 Me Et α-Me-4-MeO-benzyl 74 Me Et 4-MeO-PhSO₂ 75 Me Et 4-pyridylCH₂

TABLE 4 No R¹ R² R³ 76 Me allyl Me 77 Me allyl Et 78 Me allyl n-Pr 79 Me allyl i-Pr 80 Me allyl allyl 81 Me allyl cinnamyl 82 Me allyl 2-propynyl 83 Me allyl 2-butynyl 84 Me allyl 2-pyridyl 85 Me allyl benzyl 86 Me allyl 2-Cl-benzyl 87 Me allyl 3-Cl-benzyl 88 Me allyl 4-Cl-benzyl 89 Me allyl 2-Me-benzyl 90 Me allyl 3-Me-benzyl 91 Me allyl 4-Me-benzyl 92 Me allyl 2-MeO-benzyl 93 Me allyl 3-MeO-benzyl 94 Me allyl 4-MeO-benzyl 95 Me allyl 2-Cl-4-MeO-benzyl 96 Me allyl 3,4-(Cl)₂-benzyl 97 Me allyl 2-Me-4-MeO-benzyl 98 Me allyl α-Me-4-MeO-benzyl 99 Me allyl 4-MeO-PhSO₂ 100 Me allyl 4-pyridylCH₂

TABLE 5 No R¹ R² R³ 101 Me cinnamyl Me 102 Me cinnamyl Et 103 Me cinnamyl n-Pr 104 Me cinnamyl i-Pr 105 Me cinnamyl allyl 106 Me cinnamyl cinnamyl 107 Me cinnamyl 2-propynyl 108 Me cinnamyl 2-butynyl 109 Me cinnamyl 2-pyridyl 110 Me cinnamyl benzyl 111 Me cinnamyl 2-Cl-benzyl 112 Me cinnamyl 3-Cl-benzyl 113 Me cinnamyl 4-Cl-benzyl 114 Me cinnamyl 2-Me-benzyl 115 Me cinnamyl 3-Me-benzyl 116 Me cinnamyl 4-Me-benzyl 117 Me cinnamyl 2-MeO-benzyl 118 Me cinnamyl 3-MeO-benzyl 119 Me cinnamyl 4-MeO-benzyl 120 Me cinnamyl 2-Cl-4-MeO-benzyl 121 Me cinnamyl 3,4-(Cl)₂-benzyl 122 Me cinnamyl 2-Me-4-MeO-benzyl 123 Me cinnamyl α-Me-4-MeO-benzyl 124 Me cinnamyl 4-MeO-PhSO₂ 125 Me cinnamyl 4-pyridylCH₂

TABLE 6 No R¹ R² R³ 126 Me 2-propynyl Me 127 Me 2-propynyl Et 128 Me 2-propynyl n-Pr 129 Me 2-propynyl i-Pr 130 Me 2-propynyl allyl 131 Me 2-propynyl cinnamyl 132 Me 2-propynyl 2-propynyl 133 Me 2-propynyl 2-butynyl 134 Me 2-propynyl 2-pyridyl 135 Me 2-propynyl benzyl 136 Me 2-propynyl 2-Cl-benzyl 137 Me 2-propynyl 3-Cl-benzyl 138 Me 2-propynyl 4-Cl-benzyl 139 Me 2-propynyl 2-Me-benzyl 140 Me 2-propynyl 3-Me-benzyl 141 Me 2-propynyl 4-Me-benzyl 142 Me 2-propynyl 2-MeO-benzyl 143 Me 2-propynyl 3-MeO-benzyl 144 Me 2-propynyl 4-MeO-benzyl 145 Me 2-propynyl 2-Cl-4-MeO-benzyl 146 Me 2-propynyl 3,4-(Cl)₂-benzyl 147 Me 2-propynyl 2-Me-4-MeO-benzyl 148 Me 2-propynyl α-Me-4-MeO-benzyl 149 Me 2-propynyl 4-MeO-PhSO₂ 150 Me 2-propynyl 4-pyridylCH₂

TABLE 7 No R¹ R² R³ 151 Me 2-pyridyl Me 152 Me 2-pyridyl Et 153 Me 2-pyridyl n-Pr 154 Me 2-pyridyl i-Pr 155 Me 2-pyridyl allyl 156 Me 2-pyridyl cinnamyl 157 Me 2-pyridyl 2-propynyl 158 Me 2-pyridyl 2-butynyl 159 Me 2-pyridyl 2-pyridyl 160 Me 2-pyridyl benzyl 161 Me 2-pyridyl 2-Cl-benzyl 162 Me 2-pyridyl 3-Cl-benzyl 163 Me 2-pyridyl 4-Cl-benzyl 164 Me 2-pyridyl 2-Me-benzyl 165 Me 2-pyridyl 3-Me-benzyl 166 Me 2-pyridyl 4-Me-benzyl 167 Me 2-pyridyl 2-MeO-benzyl 168 Me 2-pyridyl 3-MeO-benzyl 169 Me 2-pyridyl 4-MeO-benzyl 170 Me 2-pyridyl 2-Cl-4-MeO-benzyl 171 Me 2-pyridyl 3,4-(Cl)₂-benzyl 172 Me 2-pyridyl 2-Me-4-MeO-benzyl 173 Me 2-pyridyl α-Me-4-MeO-benzyl 174 Me 2-pyridyl 4-MeO-PhSO₂ 175 Me 2-pyridyl 4-pyridylCH₂

TABLE 8 No R¹ R² R³ 176 Me benzyl Me 177 Me benzyl Et 178 Me benzyl n-Pr 179 Me benzyl i-Pr 180 Me benzyl allyl 181 Me benzyl cinnamyl 182 Me benzyl 2-propynyl 183 Me benzyl 2-butynyl 184 Me benzyl 2-pyridyl 185 Me benzyl benzyl 186 Me benzyl 2-Cl-benzyl 187 Me benzyl 3-Cl-benzyl 188 Me benzyl 4-Cl-benzyl 189 Me benzyl 2-Me-benzyl 190 Me benzyl 3-Me-benzyl 191 Me benzyl 4-Me-benzyl 192 Me benzyl 2-MeO-benzyl 193 Me benzyl 3-MeO-benzyl 194 Me benzyl 4-MeO-benzyl 195 Me benzyl 2-Cl-4-MeO-benzyl 196 Me benzyl 3,4-(Cl)₂-benzyl 197 Me benzyl 2-Me-4-MeO-benzyl 198 Me benzyl α-Me-4-MeO-benzyl 199 Me benzyl 4-MeO-PhSO₂ 200 Me benzyl 4-pyridylCH₂

TABLE 9 No R¹ R² R³ 201 Me 2-butynyl Me 202 Me 2-butynyl Et 203 Me 2-butynyl n-Pr 204 Me 2-butynyl i-Pr 205 Me 2-butynyl allyl 206 Me 2-butynyl cinnamyl 207 Me 2-butynyl 2-propynyl 208 Me 2-butynyl 2-butynyl 209 Me 2-butynyl 2-pyridyl 210 Me 2-butynyl benzyl 211 Me 2-butynyl 2-Cl-benzyl 212 Me 2-butynyl 3-Cl-benzyl 213 Me 2-butynyl 4-Cl-benzyl 214 Me 2-butynyl 2-Me-benzyl 215 Me 2-butynyl 3-Me-benzyl 216 Me 2-butynyl 4-Me-benzyl 217 Me 2-butynyl 2-MeO-benzyl 218 Me 2-butynyl 3-MeO-benzyl 219 Me 2-butynyl 4-MeO-benzyl 220 Me 2-butynyl 2-Cl-4-MeO-benzyl 221 Me 2-butynyl 3,4-(Cl)₂-benzyl 222 Me 2-butynyl 2-Me-4-MeO-benzyl 223 Me 2-butynyl α-Me-4-MeO-benzyl 224 Me 2-butynyl 4-MeO-PhSO₂ 225 Me 2-butynyl 4-pyridylCH₂

TABLE 10 No R¹ R² R³ 226 Me Ph Me 227 Me Ph Et 228 Me Ph n-Pr 229 Me Ph i-Pr 230 Me Ph allyl 231 Me Ph cinnamyl 232 Me Ph 2-propynyl 233 Me Ph 2-butynyl 234 Me Ph 2-pyridyl 235 Me Ph benzyl 236 Me Ph 2-Cl-benzyl 237 Me Ph 3-Cl-benzyl 238 Me Ph 4-Cl-benzyl 239 Me Ph 2-Me-benzyl 240 Me Ph 3-Me-benzyl 241 Me Ph 4-Me-benzyl 242 Me Ph 2-MeO-benzyl 243 Me Ph 3-MeO-benzyl 244 Me Ph 4-MeO-benzyl 245 Me Ph 2-Cl-4-MeO-benzyl 246 Me Ph 3,4-(Cl)₂-benzyl 247 Me Ph 2-Me-4-MeO-benzyl 248 Me Ph α-Me-4-MeO-benzyl 249 Me Ph 4-MeO-PhSO₂ 250 Me Ph 4-pyridylCH₂

TABLE 11 No R¹ R² R³ 251 Me 2-Cl-benzyl Me 252 Me 2-Cl-benzyl Et 253 Me 2-Cl-benzyl n-Pr 254 Me 2-Cl-benzyl i-Pr 255 Me 2-Cl-benzyl allyl 256 Me 2-Cl-benzyl cinnamyl 257 Me 2-Cl-benzyl 2-propynyl 258 Me 2-Cl-benzyl 2-butynyl 259 Me 2-Cl-benzyl 2-pyridyl 260 Me 2-Cl-benzyl benzyl 261 Me 2-Cl-benzyl 2-Cl-benzyl 262 Me 2-Cl-benzyl 3-Cl-benzyl 263 Me 2-Cl-benzyl 4-Cl-benzyl 264 Me 2-Cl-benzyl 2-Me-benzyl 265 Me 2-Cl-benzyl 3-Me-benzyl 266 Me 2-Cl-benzyl 4-Me-benzyl 267 Me 2-Cl-benzyl 2-MeO-benzyl 268 Me 2-Cl-benzyl 3-MeO-benzyl 269 Me 2-Cl-benzyl 4-MeO-benzyl 270 Me 2-Cl-benzyl 2-Cl-4-MeO-benzyl 271 Me 2-Cl-benzyl 3,4-(Cl)₂-benzyl 272 Me 2-Cl-benzyl 2-Me-4-MeO-benzyl 273 Me 2-Cl-benzyl α-Me-4-MeO-benzyl 274 Me 2-Cl-benzyl 4-MeO-PhSO₂ 275 Me 2-Cl-benzyl 4-pyridylCH₂

TABLE 12 No R¹ R² R³ 276 Me 3-Cl-benzyl Me 277 Me 3-Cl-benzyl Et 278 Me 3-Cl-benzyl n-Pr 279 Me 3-Cl-benzyl i-Pr 280 Me 3-Cl-benzyl allyl 281 Me 3-Cl-benzyl cinnamyl 282 Me 3-Cl-benzyl 2-propynyl 283 Me 3-Cl-benzyl 2-butynyl 284 Me 3-Cl-benzyl 2-pyridyl 285 Me 3-Cl-benzyl benzyl 286 Me 3-Cl-benzyl 2-Cl-benzyl 287 Me 3-Cl-benzyl 3-Cl-benzyl 288 Me 3-Cl-benzyl 4-Cl-benzyl 289 Me 3-Cl-benzyl 2-Me-benzyl 290 Me 3-Cl-benzyl 3-Me-benzyl 291 Me 3-Cl-benzyl 4-Me-benzyl 292 Me 3-Cl-benzyl 2-MeO-benzyl 293 Me 3-Cl-benzyl 3-MeO-benzyl 294 Me 3-Cl-benzyl 4-MeO-benzyl 295 Me 3-Cl-benzyl 2-Cl-4-MeO-benzyl 296 Me 3-Cl-benzyl 3,4-(Cl)₂-benzyl 297 Me 3-Cl-benzyl 2-Me-4-MeO-benzyl 298 Me 3-Cl-benzyl α-Me-4-MeO-benzyl 299 Me 3-Cl-benzyl 4-MeO-PhSO₂ 300 Me 3-Cl-benzyl 4-pyridylCH₂

TABLE 13 No R¹ R² R³ 301 Me 4-Cl-benzyl Me 302 Me 4-Cl-benzyl Et 303 Me 4-Cl-benzyl n-Pr 304 Me 4-Cl-benzyl i-Pr 305 Me 4-Cl-benzyl allyl 306 Me 4-Cl-benzyl cinnamyl 307 Me 4-Cl-benzyl 2-propynyl 308 Me 4-Cl-benzyl 2-butynyl 309 Me 4-Cl-benzyl 2-pyridyl 310 Me 4-Cl-benzyl benzyl 311 Me 4-Cl-benzyl 2-Cl-benzyl 312 Me 4-Cl-benzyl 3-Cl-benzyl 313 Me 4-Cl-benzyl 4-Cl-benzyl 314 Me 4-Cl-benzyl 2-Me-benzyl 315 Me 4-Cl-benzyl 3-Me-benzyl 316 Me 4-Cl-benzyl 4-Me-benzyl 317 Me 4-Cl-benzyl 2-MeO-benzyl 318 Me 4-Cl-benzyl 3-MeO-benzyl 319 Me 4-Cl-benzyl 4-MeO-benzyl 320 Me 4-Cl-benzyl 2-Cl-4-MeO-benzyl 321 Me 4-Cl-benzyl 3,4-(Cl)₂-benzyl 322 Me 4-Cl-benzyl 2-Me-4-MeO-benzyl 323 Me 4-Cl-benzyl α-Me-4-MeO-benzyl 324 Me 4-Cl-benzyl 4-MeO-PhSO₂ 325 Me 4-Cl-benzyl 4-pyridylCH₂

TABLE 14 No R¹ R² R³ 326 Me 2-Me-benzyl Me 327 Me 2-Me-benzyl Et 328 Me 2-Me-benzyl n-Pr 329 Me 2-Me-benzyl i-Pr 330 Me 2-Me-benzyl allyl 331 Me 2-Me-benzyl cinnamyl 332 Me 2-Me-benzyl 2-propynyl 333 Me 2-Me-benzyl 2-butynyl 334 Me 2-Me-benzyl 2-pyridyl 335 Me 2-Me-benzyl benzyl 336 Me 2-Me-benzyl 2-Cl-benzyl 337 Me 2-Me-benzyl 3-Cl-benzyl 338 Me 2-Me-benzyl 4-Cl-benzyl 339 Me 2-Me-benzyl 2-Me-benzyl 340 Me 2-Me-benzyl 3-Me-benzyl 341 Me 2-Me-benzyl 4-Me-benzyl 342 Me 2-Me-benzyl 2-MeO-benzyl 343 Me 2-Me-benzyl 3-MeO-benzyl 344 Me 2-Me-benzyl 4-MeO-benzyl 345 Me 2-Me-benzyl 2-Cl-4-MeO-benzyl 346 Me 2-Me-benzyl 3,4-(Cl)₂-benzyl 347 Me 2-Me-benzyl 2-Me-4-MeO-benzyl 348 Me 2-Me-benzyl α-Me-4-MeO-benzyl 349 Me 2-Me-benzyl 4-MeO-PhSO₂ 350 Me 2-Me-benzyl 4-pyridylCH₂

TABLE 15 No R¹ R² R³ 351 Me 3-Me-benzyl Me 352 Me 3-Me-benzyl Et 353 Me 3-Me-benzyl n-Pr 354 Me 3-Me-benzyl i-Pr 355 Me 3-Me-benzyl allyl 356 Me 3-Me-benzyl cinnamyl 357 Me 3-Me-benzyl 2-propynyl 358 Me 3-Me-benzyl 2-butynyl 359 Me 3-Me-benzyl 2-pyridyl 360 Me 3-Me-benzyl benzyl 361 Me 3-Me-benzyl 2-Cl-benzyl 362 Me 3-Me-benzyl 3-Cl-benzyl 363 Me 3-Me-benzyl 4-Cl-benzyl 364 Me 3-Me-benzyl 2-Me-benzyl 365 Me 3-Me-benzyl 3-Me-benzyl 366 Me 3-Me-benzyl 4-Me-benzyl 367 Me 3-Me-benzyl 2-MeO-benzyl 368 Me 3-Me-benzyl 3-MeO-benzyl 369 Me 3-Me-benzyl 4-MeO-benzyl 370 Me 3-Me-benzyl 2-Cl-4-MeO-benzyl 371 Me 3-Me-benzyl 3,4-(Cl)₂-benzyl 372 Me 3-Me-benzyl 2-Me-4-MeO-benzyl 373 Me 3-Me-benzyl α-Me-4-MeO-benzyl 374 Me 3-Me-benzyl 4-MeO-PhSO₂ 375 Me 3-Me-benzyl 4-pyridylCH₂

TABLE 16 No R¹ R² R³ 376 Me 4-Me-benzyl Me 377 Me 4-Me-benzyl Et 378 Me 4-Me-benzyl n-Pr 379 Me 4-Me-benzyl i-Pr 380 Me 4-Me-benzyl allyl 381 Me 4-Me-benzyl cinnamyl 382 Me 4-Me-benzyl 2-propynyl 383 Me 4-Me-benzyl 2-butynyl 384 Me 4-Me-benzyl 2-pyridyl 385 Me 4-Me-benzyl benzyl 386 Me 4-Me-benzyl 2-Cl-benzyl 387 Me 4-Me-benzyl 3-Cl-benzyl 388 Me 4-Me-benzyl 4-Cl-benzyl 389 Me 4-Me-benzyl 2-Me-benzyl 390 Me 4-Me-benzyl 3-Me-benzyl 391 Me 4-Me-benzyl 4-Me-benzyl 392 Me 4-Me-benzyl 2-MeO-benzyl 393 Me 4-Me-benzyl 3-MeO-benzyl 394 Me 4-Me-benzyl 4-MeO-benzyl 395 Me 4-Me-benzyl 2-Cl-4-MeO-benzyl 396 Me 4-Me-benzyl 3,4-(Cl)₂-benzyl 397 Me 4-Me-benzyl 2-Me-4-MeO-benzyl 398 Me 4-Me-benzyl α-Me-4-MeO-benzyl 399 Me 4-Me-benzyl 4-MeO-PhSO₂ 400 Me 4-Me-benzyl 4-pyridylCH₂

TABLE 17 No R¹ R² R³ 401 Me 2-MeO-benzyl Me 402 Me 2-MeO-benzyl Et 403 Me 2-MeO-benzyl n-Pr 404 Me 2-MeO-benzyl i-Pr 405 Me 2-MeO-benzyl allyl 406 Me 2-MeO-benzyl cinnamyl 407 Me 2-MeO-benzyl 2-propynyl 408 Me 2-MeO-benzyl 2-butynyl 409 Me 2-MeO-benzyl 2-pyridyl 410 Me 2-MeO-benzyl benzyl 411 Me 2-MeO-benzyl 2-Cl-benzyl 412 Me 2-MeO-benzyl 3-Cl-benzyl 413 Me 2-MeO-benzyl 4-Cl-benzyl 414 Me 2-MeO-benzyl 2-Me-benzyl 415 Me 2-MeO-benzyl 3-Me-benzyl 416 Me 2-MeO-benzyl 4-Me-benzyl 417 Me 2-MeO-benzyl 2-MeO-benzyl 418 Me 2-MeO-benzyl 3-MeO-benzyl 419 Me 2-MeO-benzyl 4-MeO-benzyl 420 Me 2-MeO-benzyl 2-Cl-4-MeO-benzyl 421 Me 2-MeO-benzyl 3,4-(Cl)₂-benzyl 422 Me 2-MeO-benzyl 2-Me-4-MeO-benzyl 423 Me 2-MeO-benzyl α-Me-4-MeO-benzyl 424 Me 2-MeO-benzyl 4-MeO-PhSO₂ 425 Me 2-MeO-benzyl 4-pyridylCH₂

TABLE 18 No R¹ R² R³ 426 Me 3-MeO-benzyl Me 427 Me 3-MeO-benzyl Et 428 Me 3-MeO-benzyl n-Pr 429 Me 3-MeO-benzyl i-Pr 430 Me 3-MeO-benzyl allyl 431 Me 3-MeO-benzyl cinnamyl 432 Me 3-MeO-benzyl 2-propynyl 433 Me 3-MeO-benzyl 2-butynyl 434 Me 3-MeO-benzyl 2-pyridyl 435 Me 3-MeO-benzyl benzyl 436 Me 3-MeO-benzyl 2-Cl-benzyl 437 Me 3-MeO-benzyl 3-Cl-benzyl 438 Me 3-MeO-benzyl 4-Cl-benzyl 439 Me 3-MeO-benzyl 2-Me-benzyl 440 Me 3-MeO-benzyl 3-Me-benzyl 441 Me 3-MeO-benzyl 4-Me-benzyl 442 Me 3-MeO-benzyl 2-MeO-benzyl 443 Me 3-MeO-benzyl 3-MeO-benzyl 444 Me 3-MeO-benzyl 4-MeO-benzyl 445 Me 3-MeO-benzyl 2-Cl-4-MeO-benzyl 446 Me 3-MeO-benzyl 3,4-(Cl)₂-benzyl 447 Me 3-MeO-benzyl 2-Me-4-MeO-benzyl 448 Me 3-MeO-benzyl α-Me-4-MeO-benzyl 449 Me 3-MeO-benzyl 4-MeO-PhSO₂ 450 Me 3-MeO-benzyl 4-pyridylCH₂

TABLE 19 No R¹ R² R³ 451 Me 4-MeO-benzyl Me 452 Me 4-MeO-benzyl Et 453 Me 4-MeO-benzyl n-Pr 454 Me 4-MeO-benzyl i-Pr 455 Me 4-MeO-benzyl allyl 456 Me 4-MeO-benzyl cinnamyl 457 Me 4-MeO-benzyl 2-propynyl 458 Me 4-MeO-benzyl 2-butynyl 459 Me 4-MeO-benzyl 2-pyridyl 460 Me 4-MeO-benzyl benzyl 461 Me 4-MeO-benzyl 2-Cl-benzyl 462 Me 4-MeO-benzyl 3-Cl-benzyl 463 Me 4-MeO-benzyl 4-Cl-benzyl 464 Me 4-MeO-benzyl 2-Me-benzyl 465 Me 4-MeO-benzyl 3-Me-benzyl 466 Me 4-MeO-benzyl 4-Me-benzyl 467 Me 4-MeO-benzyl 2-MeO-benzyl 468 Me 4-MeO-benzyl 3-MeO-benzyl 469 Me 4-MeO-benzyl 4-MeO-benzyl 470 Me 4-MeO-benzyl 2-Cl-4-MeO-benzyl 471 Me 4-MeO-benzyl 3,4-(Cl)₂-benzyl 472 Me 4-MeO-benzyl 2-Me-4-MeO-benzyl 473 Me 4-MeO-benzyl α-Me-4-MeO-benzyl 474 Me 4-MeO-benzyl 4-MeO-PhSO₂ 475 Me 4-MeO-benzyl 4-pyridylCH₂

TABLE 20 No R¹ R² R³ 476 Me 3,4-(Cl)₂-benzyl Me 477 Me 3,4-(Cl)₂-benzyl Et 478 Me 3,4-(Cl)₂-benzyl n-Pr 479 Me 3,4-(Cl)₂-benzyl i-Pr 480 Me 3,4-(Cl)₂-benzyl allyl 481 Me 3,4-(Cl)₂-benzyl cinnamyl 482 Me 3,4-(Cl)₂-benzyl 2-propynyl 483 Me 3,4-(Cl)₂-benzyl 2-butynyl 484 Me 3,4-(Cl)₂-benzyl 2-pyridyl 485 Me 3,4-(Cl)₂-benzyl benzyl 486 Me 3,4-(Cl)₂-benzyl 2-Cl-benzyl 487 Me 3,4-(Cl)₂-benzyl 3-Cl-benzyl 488 Me 3,4-(Cl)₂-benzyl 4-Cl-benzyl 489 Me 3,4-(Cl)₂-benzyl 2-Me-benzyl 490 Me 3,4-(Cl)₂-benzyl 3-Me-benzyl 491 Me 3,4-(Cl)₂-benzyl 4-Me-benzyl 492 Me 3,4-(Cl)₂-benzyl 2-MeO-benzyl 493 Me 3,4-(Cl)₂-benzyl 3-MeO-benzyl 494 Me 3,4-(Cl)₂-benzyl 4-MeO-benzyl 495 Me 3,4-(Cl)₂-benzyl 2-Cl-4-MeO-benzyl 496 Me 3,4-(Cl)₂-benzyl 3,4-(Cl)₂-benzyl 497 Me 3,4-(Cl)₂-benzyl 2-Me-4-MeO-benzyl 498 Me 3,4-(Cl)₂-benzyl α-Me-4-MeO-benzyl 499 Me 3,4-(Cl)₂-benzyl 4-MeO-PhSO₂ 500 Me 3,4-(Cl)₂-benzyl 4-pyridylCH₂

TABLE 21 No R¹ R² R³ 501 Me 2-Cl-4-MeO-benzyl Me 502 Me 2-Cl-4-MeO-benzyl Et 503 Me 2-Cl-4-MeO-benzyl n-Pr 504 Me 2-Cl-4-MeO-benzyl i-Pr 505 Me 2-Cl-4-MeO-benzyl allyl 506 Me 2-Cl-4-MeO-benzyl cinnamyl 507 Me 2-Cl-4-MeO-benzyl 2-propynyl 508 Me 2-Cl-4-MeO-benzyl 2-butynyl 509 Me 2-Cl-4-MeO-benzyl 2-pyridyl 510 Me 2-Cl-4-MeO-benzyl benzyl 511 Me 2-Cl-4-MeO-benzyl 2-Cl-benzyl 512 Me 2-Cl-4-MeO-benzyl 3-Cl-benzyl 513 Me 2-Cl-4-MeO-benzyl 4-Cl-benzyI 514 Me 2-Cl-4-MeO-benzyl 2-Me-benzyl 515 Me 2-Cl-4-MeO-benzyl 3-Me-benzyl 516 Me 2-Cl-4-MeO-benzyl 4-Me-benzyl 517 Me 2-Cl-4-MeO-benzyl 2-MeO-benzyl 518 Me 2-Cl-4-MeO-benzyl 3-MeO-benzyl 519 Me 2-Cl-4-MeO-benzyl 4-MeO-benzyl 520 Me 2-Cl-4-MeO-benzyl 2-Cl-4-MeO-benzyl 521 Me 2-Cl-4-MeO-benzyl 3,4-(Cl)₂-benzyl 522 Me 2-Cl-4-MeO-benzyl 2-Me-4-MeO-benzyl 523 Me 2-Cl-4-MeO-benzyl α-Me-4-MeO-benzyl 524 Me 2-Cl-4-MeO-benzyl 4-MeO-PhSO₂ 525 Me 2-Cl-4-MeO-benzyl 4-pyridylCH₂

TABLE 22 No R¹ R² R³ 526 Me 2-pyridylCH₂ Me 527 Me 2-pyridylCH₂ Et 528 Me 2-pyridylCH₂ n-Pr 529 Me 2-pyridylCH₂ i-Pr 530 Me 2-pyridylCH₂ allyl 531 Me 2-pyridylCH₂ cinnamyl 532 Me 2-pyridylCH₂ 2-propynyl 533 Me 2-pyridylCH₂ 2-butynyl 534 Me 2-pyridylCH₂ 2-pyridyl 535 Me 2-pyridylCH₂ benzyl 536 Me 2-pyridylCH₂ 2-Cl-benzyl 537 Me 2-pyridylCH₂ 3-Cl-benzyl 538 Me 2-pyridylCH₂ 4-Cl-benzyl 539 Me 2-pyridylCH₂ 2-Me-benzyl 540 Me 2-pyridylCH₂ 3-Me-benzyl 541 Me 2-pyridylCH₂ 4-Me-benzyl 542 Me 2-pyridylCH₂ 2-MeO-benzyl 543 Me 2-pyridylCH₂ 3-MeO-benzyl 544 Me 2-pyridylCH₂ 4-MeO-benzyl 545 Me 2-pyridylCH₂ 2-Cl-4-MeO-benzyl 546 Me 2-pyridylCH₂ 3,4-(Cl)₂-benzyl 547 Me 2-pyridylCH₂ 2-Me-4-MeO-benzyl 548 Me 2-pyridylCH₂ α-Me-4-MeO-benzyl 549 Me 2-pyridylCH₂ 4-MeO-PhSO₂ 550 Me 2-pyridylCH₂ 4-pyridylCH₂

TABLE 23 No R¹ R² R³ 551 Me 3-pyridylCH₂ Me 552 Me 3-pyridylCH₂ Et 553 Me 3-pyridylCH₂ n-Pr 554 Me 3-pyridylCH₂ i-Pr 555 Me 3-pyridylCH₂ allyl 556 Me 3-pyridylCH₂ cinnamyl 557 Me 3-pyridylCH₂ 2-propynyl 558 Me 3-pyridylCH₂ 2-butynyl 559 Me 3-pyridylCH₂ 2-pyridyl 560 Me 3-pyridylCH₂ benzyl 561 Me 3-pyridylCH₂ 2-Cl-benzyl 562 Me 3-pyridylCH₂ 3-Cl-benzyl 563 Me 3-pyridylCH₂ 4-Cl-benzyl 564 Me 3-pyridylCH₂ 2-Me-benzyl 565 Me 3-pyridylCH₂ 3-Me-benzyl 566 Me 3-pyridylCH₂ 4-Me-benzyl 567 Me 3-pyridylCH₂ 2-MeO-benzyl 568 Me 3-pyridylCH₂ 3-MeO-benzyl 569 Me 3-pyridylCH₂ 4-MeO-benzyl 570 Me 3-pyridylCH₂ 2-Cl-4-MeO-benzyl 571 Me 3-pyridylCH₂ 3,4-(Cl)₂-benzyl 572 Me 3-pyridylCH₂ 2-Me-4-MeO-benzyl 573 Me 3-pyridylCH₂ α-Me-4-MeO-benzyl 574 Me 3-pyridylCH₂ 4-MeO-PhSO₂ 575 Me 3-pyridylCH₂ 4-pyridylCH₂

TABLE 24 No R¹ R² R³ 576 Me 4-pyridylCH₂ Me 577 Me 4-pyridylCH₂ Et 578 Me 4-pyridylCH₂ n-Pr 579 Me 4-pyridylCH₂ i-Pr 580 Me 4-pyridylCH₂ allyl 581 Me 4-pyridylCH₂ cinnamyl 582 Me 4-pyridylCH₂ 2-propynyl 583 Me 4-pyridylCH₂ 2-butynyl 584 Me 4-pyridylCH₂ 2-pyridyl 585 Me 4-pyridylCH₂ benzyl 586 Me 4-pyridylCH₂ 2-Cl-benzyl 587 Me 4-pyridylCH₂ 3-Cl-benzyl 588 Me 4-pyridylCH₂ 4-Cl-benzyl 589 Me 4-pyridylCH₂ 2-Me-benzyl 590 Me 4-pyridylCH₂ 3-Me-benzyl 591 Me 4-pyridylCH₂ 4-Me-benzyl 592 Me 4-pyridylCH₂ 2-MeO-benzyl 593 Me 4-pyridylCH₂ 3-MeO-benzyl 594 Me 4-pyridylCH₂ 4-MeO-benzyl 595 Me 4-pyridylCH₂ 2-Cl-4-MeO-benzyl 596 Me 4-pyridylCH₂ 3,4-(Cl)₂-benzyl 597 Me 4-pyridylCH₂ 2-Me-4-MeO-benzyl 598 Me 4-pyridylCH₂ α-Me-4-MeO-benzyl 599 Me 4-pyridylCH₂ 4-MeO-PhSO₂ 600 Me 4-pyridylCH₂ 4-pyridylCH₂

TABLE 25 No R¹ R² R³ 601 Et Me Me 602 Et Me Et 603 Et Me n-Pr 604 Et Me i-Pr 605 Et Me allyl 606 Et Me cinnamyl 607 Et Me 2-propynyl 608 Et Me 2-butynyl 609 Et Me 2-pyridyl 610 Et Me benzyl 611 Et Me 2-Cl-benzyl 612 Et Me 3-Cl-benzyl 613 Et Me 4-Cl-benzyl 614 Et Me 2-Me-benzyl 615 Et Me 3-Me-benzyl 616 Et Me 4-Me-benzyl 617 Et Me 2-MeO-benzyl 618 Et Me 3-MeO-benzyl 619 Et Me 4-MeO-benzyl 620 Et Me 2-Cl-4-MeO-benzyl 621 Et Me 3,4-(Cl)₂-benzyl 622 Et Me 2-Me-4-MeO-benzyl 623 Et Me α-Me-4-MeO-benzyl 624 Et Me 4-MeO-PhSO₂ 625 Et Me 4-pyridylCH₂

TABLE 26 No R¹ R² R³ 626 Et MeOCH₂ Me 627 Et MeOCH₂ Et 628 Et MeOCH₂ n-Pr 629 Et MeOCH₂ i-Pr 630 Et MeOCH₂ allyl 631 Et MeOCH₂ cinnamyl 632 Et MeOCH₂ 2-propynyl 633 Et MeOCH₂ 2-butynyl 634 Et MeOCH₂ 2-pyridyl 635 Et MeOCH₂ benzyl 636 Et MeOCH₂ 2-Cl-benzyl 637 Et MeOCH₂ 3-Cl-benzyl 638 Et MeOCH₂ 4-Cl-benzyl 639 Et MeOCH₂ 2-Me-benzyl 640 Et MeOCH₂ 3-Me-benzyl 641 Et MeOCH₂ 4-Me-benzyl 642 Et MeOCH₂ 2-MeO-benzyl 643 Et MeOCH₂ 3-MeO-benzyl 644 Et MeOCH₂ 4-MeO-benzyl 645 Et MeOCH₂ 2-Cl-4-MeO-benzyl 646 Et MeOCH₂ 3,4-(Cl)₂-benzyl 647 Et MeOCH₂ 2-Me-4-MeO-benzyl 648 Et MeOCH₂ α-Me-4-MeO-benzyl 649 Et MeOCH₂ 4-MeO-PhSO₂ 650 Et MeOCH₂ 4-pyridylCH₂

TABLE 27 No R¹ R² R³ 651 Et Et Me 652 Et Et Et 653 Et Et n-Pr 654 Et Et i-Pr 655 Et Et allyl 656 Et Et cinnamyl 657 Et Et 2-propynyl 658 Et Et 2-butynyl 659 Et Et 2-pyridyl 660 Et Et benzyl 661 Et Et 2-Cl-benzyl 662 Et Et 3-Cl-benzyl 663 Et Et 4-Cl-benzyl 664 Et Et 2-Me-benzyl 665 Et Et 3-Me-benzyl 666 Et Et 4-Me-benzyl 667 Et Et 2-MeO-benzyl 668 Et Et 3-MeO-benzyl 669 Et Et 4-MeO-benzyl 670 Et Et 2-Cl-4-MeO-benzyl 671 Et Et 3,4-(Cl)₂-benzyl 672 Et Et 2-Me-4-MeO-benzyl 673 Et Et α-Me-4-MeO-benzyl 674 Et Et 4-MeO-PhSO₂ 675 Et Et 4-pyridylCH₂

TABLE 28 No R¹ R² R³ 676 Et allyl Me 677 Et allyl Et 678 Et allyl n-Pr 679 Et allyl i-Pr 680 Et allyl allyl 681 Et allyl cinnamyl 682 Et allyl 2-propynyl 683 Et allyl 2-butynyl 684 Et allyl 2-pyridyl 685 Et allyl benzyl 686 Et allyl 2-Cl-benzyl 687 Et allyl 3-Cl-benzyl 688 Et allyl 4-Cl-benzyl 689 Et allyl 2-Me-benzyl 690 Et allyl 3-Me-benzyl 691 Et allyl 4-Me-benzyl 692 Et allyl 2-MeO-benzyl 693 Et allyl 3-MeO-benzyl 694 Et allyl 4-MeO-benzyl 695 Et allyl 2-Cl-4-MeO-benzyl 696 Et allyl 3,4-(Cl)₂-benzyl 697 Et allyl 2-Me-4-MeO-benzyl 698 Et allyl α-Me-4-MeO-benzyl 699 Et allyl 4-MeO-PhSO₂ 700 Et allyl 4-pyridylCH₂

TABLE 29 No R¹ R² R³ 701 Et cinnamyl Me 702 Et cinnamyl Et 703 Et cinnamyl n-Pr 704 Et cinnamyl i-Pr 705 Et cinnamyl allyl 706 Et cinnamyl cinnamyl 707 Et cinnamyl 2-propynyl 708 Et cinnamyl 2-butynyl 709 Et cinnamyl 2-pyridyl 710 Et cinnamyl benzyl 711 Et cinnamyl 2-Cl-benzyl 712 Et cinnamyl 3-Cl-benzyl 713 Et cinnamyl 4-Cl-benzyl 714 Et cinnamyl 2-Me-benzyl 715 Et cinnamyl 3-Me-benzyl 716 Et cinnamyl 4-Me-benzyl 717 Et cinnamyl 2-MeO-benzyl 718 Et cinnamyl 3-MeO-benzyl 719 Et cinnamyl 4-MeO-benzyl 720 Et cinnamyl 2-Cl-4-MeO-benzyl 721 Et cinnamyl 3,4-(Cl)₂-benzyl 722 Et cinnamyl 2-Me-4-MeO-benzyl 723 Et cinnamyl α-Me-4-MeO-benzyl 724 Et cinnamyl 4-MeO-PhSO₂ 725 Et cinnamyl 4-pyridylCH₂

TABLE 30 No R¹ R² R³ 726 Et 2-propynyl Me 727 Et 2-propynyl Et 728 Et 2-propynyl n-Pr 729 Et 2-propynyl i-Pr 730 Et 2-propynyl allyl 731 Et 2-propynyl cinnamyl 732 Et 2-propynyl 2-propynyl 733 Et 2-propynyl 2-butynyl 734 Et 2-propynyl 2-pyridyl 735 Et 2-propynyl benzyl 736 Et 2-propynyl 2-Cl-benzyl 737 Et 2-propynyl 3-Cl-benzyl 738 Et 2-propynyl 4-Cl-benzyl 739 Et 2-propynyl 2-Me-benzyl 740 Et 2-propynyl 3-Me-benzyl 741 Et 2-propynyl 4-Me-benzyl 742 Et 2-propynyl 2-MeO-benzyl 743 Et 2-propynyl 3-MeO-benzyl 744 Et 2-propynyl 4-MeO-benzyl 745 Et 2-propynyl 2-Cl-4-MeO-benzyl 746 Et 2-propynyl 3,4-(Cl)₂-benzyl 747 Et 2-propynyl 2-Me-4-MeO-benzyl 748 Et 2-propynyl α-Me-4-MeO-benzyl 749 Et 2-propynyl 4-MeO-PhSO₂ 750 Et 2-propynyl 4-pyridylCH₂

TABLE 31 No R¹ R² R³ 751 Et 2-pyridyl Me 752 Et 2-pyridyl Et 753 Et 2-pyridyl n-Pr 754 Et 2-pyridyl i-Pr 755 Et 2-pyridyl allyl 756 Et 2-pyridyl cinnamyl 757 Et 2-pyridyl 2-propynyl 758 Et 2-pyridyl 2-butynyl 759 Et 2-pyridyl 2-pyridyl 760 Et 2-pyridyl benzyl 761 Et 2-pyridyl 2-Cl-benzyl 762 Et 2-pyridyl 3-Cl-benzyl 763 Et 2-pyridyl 4-Cl-benzyl 764 Et 2-pyridyl 2-Me-benzyl 765 Et 2-pyridyl 3-Me-benzyl 766 Et 2-pyridyl 4-Me-benzyl 767 Et 2-pyridyl 2-MeO-benzyl 768 Et 2-pyridyl 3-MeO-benzyl 769 Et 2-pyridyl 4-MeO-benzyl 770 Et 2-pyridyl 2-Cl-4-MeO-benzyl 771 Et 2-pyridyl 3,4-(Cl)₂-benzyl 772 Et 2-pyridyl 2-Me-4-MeO-benzyl 773 Et 2-pyridyl α-Me-4-MeO-benzyl 774 Et 2-pyridyl 4-MeO-PhSO₂ 775 Et 2-pyridyl 4-pyridylCH₂

TABLE 32 No R¹ R² R³ 776 Et benzyl Me 777 Et benzyl Et 778 Et benzyl n-Pr 779 Et benzyl i-Pr 780 Et benzyl allyl 781 Et benzyl cinnamyl 782 Et benzyl 2-propynyl 783 Et benzyl 2-butynyl 784 Et benzyl 2-pyridyl 785 Et benzyl benzyl 786 Et benzyl 2-Cl-benzyl 787 Et benzyl 3-Cl-benzyl 788 Et benzyl 4-Cl-benzyl 789 Et benzyl 2-Me-benzyl 790 Et benzyl 3-Me-benzyl 791 Et benzyl 4-Me-benzyl 792 Et benzyl 2-MeO-benzyl 793 Et benzyl 3-MeO-benzyl 794 Et benzyl 4-MeO-benzyl 795 Et benzyl 2-Cl-4-MeO-benzyl 796 Et benzyl 3,4-(Cl)₂-benzyl 797 Et benzyl 2-Me-4-MeO-benzyl 798 Et benzyl α-Me-4-MeO-benzyl 799 Et benzyl 4-MeO-PhSO₂ 800 Et benzyl 4-pyridylCH₂

TABLE 33 No R¹ R² R³ 801 Et 2-butynyl Me 802 Et 2-butynyl Et 803 Et 2-butynyl n-Pr 804 Et 2-butynyl i-Pr 805 Et 2-butynyl allyl 806 Et 2-butynyl cinnamyl 807 Et 2-butynyl 2-propynyl 808 Et 2-butynyl 2-butynyl 809 Et 2-butynyl 2-pyridyl 810 Et 2-butynyl benzyl 811 Et 2-butynyl 2-Cl-benzyl 812 Et 2-butynyl 3-Cl-benzyl 813 Et 2-butynyl 4-Cl-benzyl 814 Et 2-butynyl 2-Me-benzyl 815 Et 2-butynyl 3-Me-benzyl 816 Et 2-butynyl 4-Me-benzyl 817 Et 2-butynyl 2-MeO-benzyl 818 Et 2-butynyl 3-MeO-benzyl 819 Et 2-butynyl 4-MeO-benzyl 820 Et 2-butynyl 2-Cl-4-MeO-benzyl 821 Et 2-butynyl 3,4-(Cl)₂-benzyl 822 Et 2-butynyl 2-Me-4-MeO-benzyl 823 Et 2-butynyl α-Me-4-MeO-benzyl 824 Et 2-butynyl 4-MeO-PhSO₂ 825 Et 2-butynyl 4-pyridylCH₂

TABLE 34 No R¹ R² R³ 826 Et Ph Me 827 Et Ph Et 828 Et Ph n-Pr 829 Et Ph i-Pr 830 Et Ph allyl 831 Et Ph cinnamyl 832 Et Ph 2-propynyl 833 Et Ph 2-butynyl 834 Et Ph 2-pyridyl 835 Et Ph benzyl 836 Et Ph 2-Cl-benzyl 837 Et Ph 3-Cl-benzyl 838 Et Ph 4-Cl-benzyl 839 Et Ph 2-Me-benzyl 840 Et Ph 3-Me-benzyl 841 Et Ph 4-Me-benzyl 842 Et Ph 2-MeO-benzyl 843 Et Ph 3-MeO-benzyl 844 Et Ph 4-MeO-benzyl 845 Et Ph 2-Cl-4-MeO-benzyl 846 Et Ph 3,4-(Cl)₂-benzyl 847 Et Ph 2-Me-4-MeO-benzyl 848 Et Ph α-Me-4-MeO-benzyl 849 Et Ph 4-MeO-PhSO₂ 850 Et Ph 4-pyridylCH₂

TABLE 35 No R¹ R² R³ 851 Et 2-Cl-benzyl Me 852 Et 2-Cl-benzyl Et 853 Et 2-Cl-benzyl n-Pr 854 Et 2-Cl-benzyl i-Pr 855 Et 2-Cl-benzyl allyl 856 Et 2-Cl-benzyl cinnamyl 857 Et 2-Cl-benzyl 2-propynyl 858 Et 2-Cl-benzyl 2-butynyl 859 Et 2-Cl-benzyl 2-pyridyl 860 Et 2-Cl-benzyl benzyl 861 Et 2-Cl-benzyl 2-Cl-benzyl 862 Et 2-Cl-benzyl 3-Cl-benzyl 863 Et 2-Cl-benzyl 4-Cl-benzyl 864 Et 2-Cl-benzyl 2-Me-benzyl 865 Et 2-Cl-benzyl 3-Me-benzyl 866 Et 2-Cl-benzyl 4-Me-benzyl 867 Et 2-Cl-benzyl 2-MeO-benzyl 868 Et 2-Cl-benzyl 3-MeO-benzyl 869 Et 2-Cl-benzyl 4-MeO-benzyl 870 Et 2-Cl-benzyl 2-Cl-4-MeO-benzyl 871 Et 2-Cl-benzyl 3,4-(Cl)₂-benzyl 872 Et 2-Cl-benzyl 2-Me-4-MeO-benzyl 873 Et 2-Cl-benzyl α-Me-4-MeO-benzyl 874 Et 2-Cl-benzyl 4-MeO-PhSO₂ 875 Et 2-Cl-benzyl 4-pyridylCH₂

TABLE 36 No R¹ R² R³ 876 Et 3-Cl-benzyl Me 877 Et 3-Cl-benzyl Et 878 Et 3-Cl-benzyl n-Pr 879 Et 3-Cl-benzyl i-Pr 880 Et 3-Cl-benzyl allyl 881 Et 3-Cl-benzyl cinnamyl 882 Et 3-Cl-benzyl 2-propynyl 883 Et 3-Cl-benzyl 2-butynyl 884 Et 3-Cl-benzyl 2-pyridyl 885 Et 3-Cl-benzyl benzyl 886 Et 3-Cl-benzyl 2-Cl-benzyl 887 Et 3-Cl-benzyl 3-Cl-benzyl 888 Et 3-Cl-benzyl 4-Cl-benzyl 889 Et 3-Cl-benzyl 2-Me-benzyl 890 Et 3-Cl-benzyl 3-Me-benzyl 891 Et 3-Cl-benzyl 4-Me-benzyl 892 Et 3-Cl-benzyl 2-MeO-benzyl 893 Et 3-Cl-benzyl 3-MeO-benzyl 894 Et 3-Cl-benzyl 4-MeO-benzyl 895 Et 3-Cl-benzyl 2-Cl-4-MeO-benzyl 896 Et 3-Cl-benzyl 3,4-(Cl)₂-benzyl 897 Et 3-Cl-benzyl 2-Me-4-MeO-benzyl 898 Et 3-Cl-benzyl α-Me-4-MeO-benzyl 899 Et 3-Cl-benzyl 4-MeO-PhSO₂ 900 Et 3-Cl-benzyl 4-pyridylCH₂

TABLE 37 No R¹ R² R³ 901 Et 4-Cl-benzyl Me 902 Et 4-Cl-benzyl Et 903 Et 4-Cl-benzyl n-Pr 904 Et 4-Cl-benzyl i-Pr 905 Et 4-Cl-benzyl allyl 906 Et 4-Cl-benzyl cinnamyl 907 Et 4-Cl-benzyl 2-propynyl 908 Et 4-Cl-benzyl 2-butynyl 909 Et 4-Cl-benzyl 2-pyridyl 910 Et 4-Cl-benzyl benzyl 911 Et 4-Cl-benzyl 2-Cl-benzyl 912 Et 4-Cl-benzyl 3-Cl-benzyl 913 Et 4-Cl-benzyl 4-Cl-benzyl 914 Et 4-Cl-benzyl 2-Me-benzyl 915 Et 4-Cl-benzyl 3-Me-benzyl 916 Et 4-Cl-benzyl 4-Me-benzyl 917 Et 4-Cl-benzyl 2-MeO-benzyl 918 Et 4-Cl-benzyl 3-MeO-benzyl 919 Et 4-Cl-benzyl 4-MeO-benzyl 920 Et 4-Cl-benzyl 2-Cl-4-MeO-benzyl 921 Et 4-Cl-benzyl 3,4-(Cl)₂-benzyl 922 Et 4-Cl-benzyl 2-Me-4-MeO-benzyl 923 Et 4-Cl-benzyl α-Me-4-MeO-benzyl 924 Et 4-Cl-benzyl 4-MeO-PhSO₂ 925 Et 4-Cl-benzyl 4-pyridylCH₂

TABLE 38 No R¹ R² R³ 926 Et 2-Me-benzyl Me 927 Et 2-Me-benzyl Et 928 Et 2-Me-benzyl n-Pr 929 Et 2-Me-benzyl i-Pr 930 Et 2-Me-benzyl allyl 931 Et 2-Me-benzyl cinnamyl 932 Et 2-Me-benzyl 2-propynyl 933 Et 2-Me-benzyl 2-butynyl 934 Et 2-Me-benzyl 2-pyridyl 935 Et 2-Me-benzyl benzyl 936 Et 2-Me-benzyl 2-Cl-benzyl 937 Et 2-Me-benzyl 3-Cl-benzyl 938 Et 2-Me-benzyl 4-Cl-benzyl 939 Et 2-Me-benzyl 2-Me-benzyl 940 Et 2-Me-benzyl 3-Me-benzyl 941 Et 2-Me-benzyl 4-Me-benzyl 942 Et 2-Me-benzyl 2-MeO-benzyl 943 Et 2-Me-benzyl 3-MeO-benzyl 944 Et 2-Me-benzyl 4-MeO-benzyl 945 Et 2-Me-benzyl 2-Cl-4-MeO-benzyl 946 Et 2-Me-benzyl 3,4-(Cl)₂-benzyl 947 Et 2-Me-benzyl 2-Me-4-MeO-benzyl 948 Et 2-Me-benzyl α-Me-4-MeO-benzyl 949 Et 2-Me-benzyl 4-MeO-PhSO₂ 950 Et 2-Me-benzyl 4-pyridylCH₂

TABLE 39 No R¹ R² R³ 951 Et 3-Me-benzyl Me 952 Et 3-Me-benzyl Et 953 Et 3-Me-benzyl n-Pr 954 Et 3-Me-benzyl i-Pr 955 Et 3-Me-benzyl allyl 956 Et 3-Me-benzyl cinnamyl 957 Et 3-Me-benzyl 2-propynyl 958 Et 3-Me-benzyl 2-butynyl 959 Et 3-Me-benzyl 2-pyridyl 960 Et 3-Me-benzyl benzyl 961 Et 3-Me-benzyl 2-Cl-benzyl 962 Et 3-Me-benzyl 3-Cl-benzyl 963 Et 3-Me-benzyl 4-Cl-benzyl 964 Et 3-Me-benzyl 2-Me-benzyl 965 Et 3-Me-benzyl 3-Me-benzyl 966 Et 3-Me-benzyl 4-Me-benzyl 967 Et 3-Me-benzyl 2-MeO-benzyl 968 Et 3-Me-benzyl 3-MeO-benzyI 969 Et 3-Me-benzyl 4-MeO-benzyl 970 Et 3-Me-benzyl 2-Cl-4-MeO-benzyl 971 Et 3-Me-benzyl 3,4-(Cl)₂-benzyl 972 Et 3-Me-benzyl 2-Me-4-MeO-benzyl 973 Et 3-Me-benzyl α-Me-4-MeO-benzyl 974 Et 3-Me-benzyl 4-MeO-PhSO₂ 975 Et 3-Me-benzyl 4-pyridylCH₂

TABLE 40 No R¹ R² R³ 976 Et 4-Me-benzyl Me 977 Et 4-Me-benzyl Et 978 Et 4-Me-benzyl n-Pr 979 Et 4-Me-benzyl i-Pr 980 Et 4-Me-benzyl allyl 981 Et 4-Me-benzyl cinnamyl 982 Et 4-Me-benzyl 2-propynyl 983 Et 4-Me-benzyl 2-butynyl 984 Et 4-Me-benzyl 2-pyridyl 985 Et 4-Me-benzyl benzyl 986 Et 4-Me-benzyl 2-Cl-benzyl 987 Et 4-Me-benzyl 3-Cl-benzyl 988 Et 4-Me-benzyl 4-Cl-benzyl 989 Et 4-Me-benzyl 2-Me-benzyl 990 Et 4-Me-benzyl 3-Me-benzyl 991 Et 4-Me-benzyl 4-Me-benzyl 992 Et 4-Me-benzyl 2-MeO-benzyl 993 Et 4-Me-benzyl 3-MeO-benzyl 994 Et 4-Me-benzyl 4-MeO-benzyl 995 Et 4-Me-benzyl 2-Cl-4-MeO-benzyl 996 Et 4-Me-benzyl 3,4-(Cl)₂-benzyl 997 Et 4-Me-benzyl 2-Me-4-MeO-benzyl 998 Et 4-Me-benzyl α-Me-4-MeO-benzyl 999 Et 4-Me-benzyl 4-MeO-PhSO₂ 1000 Et 4-Me-benzyl 4-pyridylCH₂

TABLE 41 No R¹ R² R³ 1001 Et 2-MeO-benzyl Me 1002 Et 2-MeO-benzyl Et 1003 Et 2-MeO-benzyl n-Pr 1004 Et 2-MeO-benzyl i-Pr 1005 Et 2-MeO-benzyl allyl 1006 Et 2-MeO-benzyl cinnamyl 1007 Et 2-MeO-benzyl 2-propynyl 1008 Et 2-MeO-benzyl 2-butynyl 1009 Et 2-MeO-benzyl 2-pyridyl 1010 Et 2-MeO-benzyl benzyl 1011 Et 2-MeO-benzyl 2-Cl-benzyl 1012 Et 2-MeO-benzyl 3-Cl-benzyl 1013 Et 2-MeO-benzyl 4-Cl-benzyl 1014 Et 2-MeO-benzyl 2-Me-benzyl 1015 Et 2-MeO-benzyl 3-Me-benzyl 1016 Et 2-MeO-benzyl 4-Me-benzyl 1017 Et 2-MeO-benzyl 2-MeO-benzyl 1018 Et 2-MeO-benzyl 3-MeO-benzyl 1019 Et 2-MeO-benzyl 4-MeO-benzyl 1020 Et 2-MeO-benzyl 2-Cl-4-MeO-benzyl 1021 Et 2-MeO-benzyl 3,4-(Cl)₂-benzyl 1022 Et 2-MeO-benzyl 2-Me-4-MeO-benzyl 1023 Et 2-MeO-benzyl α-Me-4-MeO-benzyl 1024 Et 2-MeO-benzyl 4-MeO-PhSO₂ 1025 Et 2-MeO-benzyl 4-pyridylCH₂

TABLE 42 No R¹ R² R³ 1026 Et 3-MeO-benzyl Me 1027 Et 3-MeO-benzyl Et 1028 Et 3-MeO-benzyl n-Pr 1029 Et 3-MeO-benzyl i-Pr 1030 Et 3-MeO-benzyl aiiyi 1031 Et 3-MeO-benzyl cinnamyl 1032 Et 3-MeO-benzyl 2-propynyl 1033 Et 3-MeO-benzyl 2-butynyl 1034 Et 3-MeO-benzyl 2-pyridyl 1035 Et 3-MeO-benzyl benzyl 1036 Et 3-MeO-benzyl 2-Cl-benzyl 1037 Et 3-MeO-benzyl 3-Cl-benzyl 1038 Et 3-MeO-benzyl. 4-Cl-benzyl 1039 Et 3-MeO-benzyl 2-Me-benzyl 1040 Et 3-MeO-benzyl 3-Me-benzyl 1041 Et 3-MeO-benzyl 4-Me-benzyl 1042 Et 3-MeO-benzyl 2-MeO-benzyl 1043 Et 3-MeO-benzyl 3-MeO-benzyl 1044 Et 3-MeO-benzyl 4-MeO-benzyl 1045 Et 3-MeO-benzyl 2-Cl-4-MeO-benzyl 1046 Et 3-MeO-benzyl 3,4-(Cl)₂-benzyl 1047 Et 3-MeO-benzyl 2-Me-4-MeO-benzyl 1048 Et 3-MeO-benzyl α-Me-4-MeO-benzyl 1049 Et 3-MeO-benzyl 4-MeO-PhSO₂ 1050 Et 3-MeO-benzyl 4-pyridylCH₂

TABLE 43 No R¹ R² R³ 1051 Et 4-MeO-benzyl Me 1052 Et 4-MeO-benzyl Et 1053 Et 4-MeO-benzyl n-Pr 1054 Et 4-MeO-benzyl i-Pr 1055 Et 4-MeO-benzyl allyl 1056 Et 4-MeO-benzyl cinnamyl 1057 Et 4-MeO-benzyl 2-propynyl 1058 Et 4-MeO-benzyl 2-butynyl 1059 Et 4-MeO-benzyl 2-pyridyl 1060 Et 4-MeO-benzyl benzyl 1061 Et 4-MeO-benzyl 2-Cl-benzyl 1062 Et 4-MeO-benzyl 3-Cl-benzyl 1063 Et 4-MeO-benzyl 4-Cl-benzyl 1064 Et 4-MeO-benzyl 2-Me-benzyl 1065 Et 4-MeO-benzyl 3-Me-benzyl 1066 Et 4-MeO-benzyl 4-Me-benzyl 1067 Et 4-MeO-benzyl 2-MeO-benzyl 1068 Et 4-MeO-benzyl 3-MeO-benzyl 1069 Et 4-MeO-benzyl 4-MeO-benzyl 1070 Et 4-MeO-benzyl 2-Cl-4-MeO-benzyl 1071 Et 4-MeO-benzyl 3,4-(Cl)₂-benzyl 1072 Et 4-MeO-benzyl 2-Me-4-MeO-benzyl 1073 Et 4-MeO-benzyl α-Me-4-MeO-benzyl 1074 Et 4-MeO-benzyl 4-MeO-PhSO₂ 1075 Et 4-MeO-benzyl 4-pyridylCH₂

TABLE 44 No R¹ R² R³ 1076 Et 3,4-(Cl)₂-benzyl Me 1077 Et 3,4-(Cl)₂-benzyl Et 1078 Et 3,4-(Cl)₂-benzyl n-Pr 1079 Et 3,4-(Cl)₂-benzyl i-Pr 1080 Et 3,4-(Cl)₂-benzyl allyl 1081 Et 3,4-(Cl)₂-benzyl cinnamyl 1082 Et 3,4-(Cl)₂-benzyl 2-propynyl 1083 Et 3,4-(Cl)₂-benzyl 2-butynyl 1084 Et 3,4-(Cl)₂-benzyl 2-pyridyl 1085 Et 3,4-(Cl)₂-benzyl benzyl 1086 Et 3,4-(Cl)₂-benzyl 2-Cl-benzyl 1087 Et 3,4-(Cl)₂-benzyl 3-Cl-benzyl 1088 Et 3,4-(Cl)₂-benzyl 4-Cl-benzyl 1089 Et 3,4-(Cl)₂-benzyl 2-Me-benzyl 1090 Et 3,4-(Cl)₂-benzyl 3-Me-benzyl 1091 Et 3,4-(Cl)₂-benzyl 4-Me-benzyl 1092 Et 3,4-(Cl)₂-benzyl 2-MeO-benzyl 1093 Et 3,4-(Cl)₂-benzyl 3-MeO-benzyl 1094 Et 3,4-(Cl)₂-benzyl 4-MeO-benzyl 1095 Et 3,4-(Cl)₂-benzyl 2-Cl-4-MeO-benzyl 1096 Et 3,4-(Cl)₂-benzyl 3,4-(Cl)₂-benzyl 1097 Et 3,4-(Cl)₂-benzyl 2-Me-4-MeO-benzyl 1098 Et 3,4-(Cl)₂-benzyl α-Me-4-MeO-benzyl 1099 Et 3,4-(Cl)₂-benzyl 4-MeO-PhSO₂ 1100 Et 3,4-(Cl)₂-benzyl 4-pyridylCH₂

TABLE 45 No R¹ R² R³ 1101 Et 2-Cl-4-MeO-benzyl Me 1102 Et 2-Cl-4-MeO-benzyl Et 1103 Et 2-Cl-4-MeO-benzyl n-Pr 1104 Et 2-Cl-4-MeO-benzyl i-Pr 1105 Et 2-Cl-4-MeO-benzyl allyl 1106 Et 2-Cl-4-MeO-benzyl cinnamyl 1107 Et 2-Cl-4-MeO-benzyl 2-propynyl 1108 Et 2-Cl-4-MeO-benzyl 2-butynyl 1109 Et 2-Cl-4-MeO-benzyl 2-pyridyl 1110 Et 2-Cl-4-MeO-benzyl benzyl 1111 Et 2-Cl-4-MeO-benzyl 2-Cl-benzyl 1112 Et 2-Cl-4-MeO-benzyl 3-Cl-benzyl 1113 Et 2-Cl-4-MeO-benzyl 4-Cl-benzyl 1114 Et 2-Cl-4-MeO-benzyl 2-Me-benzyl 1115 Et 2-Cl-4-MeO-benzyl 3-Me-benzyl 1116 Et 2-Cl-4-MeO-benzyl 4-Me-benzyl 1117 Et 2-Cl-4-MeO-benzyl 2-MeO-benzyl 1118 Et 2-Cl-4-MeO-benzyl 3-MeO-benzyl 1119 Et 2-Cl-4-MeO-benzyl 4-MeO-benzyl 1120 Et 2-Cl-4-MeO-benzyl 2-Cl-4-MeO-benzyl 1121 Et 2-Cl-4-MeO-benzyl 3,4-(Cl)₂-benzyl 1122 Et 2-Cl-4-MeO-benzyl 2-Me-4-MeO-benzyl 1123 Et 2-Cl-4-MeO-benzyl α-Me-4-MeO-benzyl 1124 Et 2-Cl-4-MeO-benzyl 4-MeO-PhSO₂ 1125 Et 2-Cl-4-MeO-benzyl 4-pyridylCH₂

TABLE 46 No R¹ R² R³ 1126 Et 2-pyridylCH₂ Me 1127 Et 2-pyridylCH₂ Et 1128 Et 2-pyridylCH₂ n-Pr 1129 Et 2-pyridylCH₂ i-Pr 1130 Et 2-pyridylCH₂ allyl 1131 Et 2-pyridylCH₂ cinnamyl 1132 Et 2-pyridylCH₂ 2-propynyl 1133 Et 2-pyridylCH₂ 2-butynyl 1134 Et 2-pyridylCH₂ 2-pyridyl 1135 Et 2-pyridylCH₂ benzyl 1136 Et 2-pyridylCH₂ 2-Cl-benzyl 1137 Et 2-pyridylCH₂ 3-Cl-benzyl 1138 Et 2-pyridylCH₂ 4-Cl-benzyl 1139 Et 2-pyridylCH₂ 2-Me-benzyl 1140 Et 2-pyridylCH₂ 3-Me-benzyl 1141 Et 2-pyridylCH₂ 4-Me-benzyl 1142 Et 2-pyridylCH₂ 2-MeO-benzyl 1143 Et 2-pyridylCH₂ 3-MeO-benzyl 1144 Et 2-pyridylCH₂ 4-MeO-benzyl 1145 Et 2-pyridylCH₂ 2-Cl-4-MeO-benzyl 1146 Et 2-pyridylCH₂ 3,4-(Cl)₂-benzyl 1147 Et 2-pyridylCH₂ 2-Me-4-MeO-benzyl 1148 Et 2-pyridylCH₂ α-Me-4-MeO-benzyl 1149 Et 2-pyridylCH₂ 4-MeO-PhSO₂ 1150 Et 2-pyridylCH₂ 4-pyridylCH₂

TABLE 47 No R¹ R² R³ 1151 Et 3-pyridylCH₂ Me 1152 Et 3-pyridylCH₂ Et 1153 Et 3-pyridylCH₂ n-Pr 1154 Et 3-pyridylCH₂ i-Pr 1155 Et 3-pyridylCH₂ allyl 1156 Et 3-pyridylCH₂ cinnamyl 1157 Et 3-pyridylCH₂ 2-propynyl 1158 Et 3-pyridylCH₂ 2-butynyl 1159 Et 3-pyridylCH₂ 2-pyridyl 1160 Et 3-pyridylCH₂ benzyl 1161 Et 3-pyridylCH₂ 2-Cl-benzyl 1162 Et 3-pyridylCH₂ 3-Cl-benzyl 1163 Et 3-pyridylCH₂ 4-Cl-benzyl 1164 Et 3-pyridylCH₂ 2-Me-benzyl 1165 Et 3-pyridylCH₂ 3-Me-benzyl 1166 Et 3-pyridylCH₂ 4-Me-benzyl 1167 Et 3-pyridylCH₂ 2-MeO-benzyl 1168 Et 3-pyridylCH₂ 3-MeO-benzyl 1169 Et 3-pyridylCH₂ 4-MeO-benzyl 1170 Et 3-pyridylCH₂ 2-Cl-4-MeO-benzyl 1171 Et 3-pyridylCH₂ 3,4-(Cl)₂-benzyl 1172 Et 3-pyridylCH₂ 2-Me-4-MeO-benzyl 1173 Et 3-pyridylCH₂ α-Me-4-MeO-benzyl 1174 Et 3-pyridylCH₂ 4-MeO-PhSO₂ 1175 Et 3-pyridylCH₂ 4-pyridylCH₂

TABLE 48 No R¹ R² R³ 1176 Et 4-pyridylCH₂ Me 1177 Et 4-pyridylCH₂ Et 1178 Et 4-pyridylCH₂ n-Pr 1179 Et 4-pyridylCH₂ i-Pr 1180 Et 4-pyridylCH₂ allyl 1181 Et 4-pyridylCH₂ cinnamyl 1182 Et 4-pyridylCH₂ 2-propynyl 1183 Et 4-pyridylCH₂ 2-butynyl 1184 Et 4-pyridylCH₂ 2-pyridyl 1185 Et 4-pyridylCH₂ benzyl 1186 Et 4-pyridylCH₂ 2-Cl-benzyl 1187 Et 4-pyridylCH₂ 3-Cl-benzyl 1188 Et 4-pyridylCH₂ 4-Cl-benzyl 1189 Et 4-pyridylCH₂ 2-Me-benzyl 1190 Et 4-pyridylCH₂ 3-Me-benzyl 1191 Et 4-pyridylCH₂ 4-Me-benzyl 1192 Et 4-pyridylCH₂ 2-MeO-benzyl 1193 Et 4-pyridylCH₂ 3-MeO-benzyl 1194 Et 4-pyridylCH₂ 4-MeO-benzyl 1195 Et 4-pyridylCH₂ 2-Cl-4-MeO-benzyl 1196 Et 4-pyridylCH₂ 3,4-(Cl)₂-benzyl 1197 Et 4-pyridylCH₂ 2-Me-4-MeO-benzyl 1198 Et 4-pyridylCH₂ α-Me-4-MeO-benzyl 1199 Et 4-pyridylCH₂ 4-MeO-PhSO₂ 1200 Et 4-pyridylCH₂ 4-pyridylCH₂

TABLE 49 No R¹ R² R³ 1201 Pr Me Me 1202 Pr Me allyl 1203 Pr Me benzyl 1204 Pr Me 2-Cl-benzyl 1205 Pr Me 4-Cl-benzyl 1206 Pr Me 2-Me-benzyl 1207 Pr Me 4-Me-benzyl 1208 Pr Me 2-Cl-4-MeO-benzyl 1209 Pr Me 2-MeO-benzyl 1210 Pr Me 4-MeO-benzyl 1211 Pr allyl Me 1212 Pr allyl allyl 1213 Pr allyl benzyl 1214 Pr allyl 2-Cl-benzyl 1215 Pr allyl 4-Cl-benzyl 1216 Pr allyl 2-Me-benzyl 1217 Pr allyl 4-Me-benzyl 1218 Pr allyl 2-Cl-4-MeO-benzyl 1219 Pr allyl 2-MeO-benzyl 1220 Pr allyl 4-MeO-benzyl 1221 Pr 2-propynyl Me 1222 Pr 2-propynyl allyl 1223 Pr 2-propynyl benzyl 1224 Pr 2-propynyl 2-Cl-benzy 1225 Pr 2-propynyl 4-Cl-benzyl

TABLE 50 No R¹ R² R³ 1226 Pr 2-propynyl 2-Me-benzyl 1227 Pr 2-propynyl 4-Me-benzyl 1228 Pr 2-propynyl 2-Cl-4-MeO-benzyl 1229 Pr 2-propynyl 2-MeO-benzyl 1230 Pr 2-propynyl 4-MeO-benzyl 1231 Pr benzyl Me 1232 Pr benzyl allyl 1233 Pr benzyl benzyl 1234 Pr benzyl 2-Cl-benzyl 1235 Pr benzyl 4-Cl-benzyl 1236 Pr benzyl 2-Me-benzyl 1237 Pr benzyl 4-Me-benzyl 1238 Pr benzyl 2-Cl-4-MeO-benzyl 1239 Pr benzyl 2-MeO-benzyl 1240 Pr benzyl 4-MeO-benzyl 1241 Pr 4-Me-benzyl Me 1242 Pr 4-Me-benzyl allyl 1243 Pr 4-Me-benzyl benzyl 1244 Pr 4-Me-benzyl 2-Cl-benzyl 1245 Pr 4-Me-benzyl 4-Cl-benzyl 1246 Pr 4-Me-benzyl 2-Me-benzyl 1247 Pr 4-Me-benzyl 4-Me-benzyl 1248 Pr 4-Me-benzyl 2-Cl-4-MeO-benzyl 1249 Pr 4-Me-benzyl 2-MeO-benzyl 1250 Pr 4-Me-benzyl 4-MeO-benzyl

TABLE 51 No R¹ R² R³ 1251 Pr 4-Cl-benzyl Me 1252 Pr 4-Cl-benzyl allyl 1253 Pr 4-Cl-benzyl benzyl 1254 Pr 4-Cl-benzyl 2-Cl-benzyl 1255 Pr 4-Cl-benzyl 4-Cl-benzyl 1256 Pr 4-Cl-benzyl 2-Me-benzyl 1257 Pr 4-Cl-benzyl 4-Me-benzyl 1258 Pr 4-Cl-benzyl 2-Cl-4-MeO-benzyl 1259 Pr 4-Cl-benzyl 2-MeO-benzyl 1260 Pr 4-Cl-benzyl 4-MeO-benzyl 1261 Pr 4-MeO-benzyl Me 1262 Pr 4-MeO-benzyl allyl 1263 Pr 4-MeO-benzyl benzyl 1264 Pr 4-MeO-benzyl 2-Cl-benzyl 1265 Pr 4-MeO-benzyl 4-Cl-benzyl 1266 Pr 4-MeO-benzyl 2-Me-benzyl 1267 Pr 4-MeO-benzyl 4-Me-benzyl 1268 Pr 4-MeO-benzyl 2-Cl-4-MeO-benzyl 1269 Pr 4-MeO-benzyl 2-MeO-benzyl 1270 Pr 4-MeO-benzyl 4-MeO-benzyl 1271 Pr 2-pyridylCH₂ Me 1272 Pr 2-pyridylCH₂ allyl 1273 Pr 2-pyridylCH₂ benzyl 1274 Pr 2-pyridylCH₂ 2-Cl-benzyl 1275 Pr 2-pyridylCH₂ 4-Cl-benzyl

TABLE 52 No R¹ R² R³ 1276 Pr 2-pyridylCH₂ 2-Me-benzyl 1277 Pr 2-pyridylCH₂ 4-Me-benzyl 1278 Pr 2-pyridylCH₂ 2-Cl-4-MeO-benzyl 1279 Pr 2-pyridylCH₂ 2-MeO-benzyl 1280 Pr 2-pyridylCH₂ 4-MeO-benzyl 1281 Pr 3-pyridylCH₂ Me 1282 Pr 3-pyridylCH₂ allyl 1283 Pr 3-pyridylCH₂ benzyl 1284 Pr 3-pyridylCH₂ 2-Cl-benzyl 1285 Pr 3-pyridylCH₂ 4-Cl-benzyl 1286 Pr 3-pyridylCH₂ 2-Me-benzyl 1287 Pr 3-pyridylCH₂ 4-Me-benzyl 1288 Pr 3-pyridylCH₂ 2-Cl-4-MeO-benzyl 1289 Pr 3-pyridylCH₂ 2-MeO-benzyl 1290 Pr 3-pyridylCH₂ 4-MeO-benzyl 1291 Pr 4-pyridylCH₂ Me 1292 Pr 4-pyridylCH₂ allyl 1293 Pr 4-pyridylCH₂ benzyl 1294 Pr 4-pyridylCH₂ 2-Cl-benzyl 1295 Pr 4-pyridylCH₂ 4-Cl-benzyl 1296 Pr 4-pyridylCH₂ 2-Me-benzyl 1297 Pr 4-pyridylCH₂ 4-Me-benzyl 1298 Pr 4-pyridylCH₂ 2-Cl-4-MeO-benzyl 1299 Pr 4-pyridylCH₂ 2-MeO-benzyl 1300 Pr 4-pyridylCH₂ 4-MeO-benzyl

TABLE 53 No R¹ R² R³ 1301 Ph Me Me 1302 Ph Me allyl 1303 Ph Me benzyl 1304 Ph Me 2-Cl-benzyl 1305 Ph Me 4-Cl-benzyl 1306 Ph Me 2-Me-benzyl 1307 Ph Me 4-Me-benzyl 1308 Ph Me 2-Cl-4-MeO-benzyl 1309 Ph Me 2-MeO-benzyl 1310 Ph Me 4-MeO-benzyl 1311 Ph allyl Me 1312 Ph allyl allyl 1313 Ph allyl benzyl 1314 Ph allyl 2-Cl-benzyl 1315 Ph allyl 4-Cl-benzyl 1316 Ph allyl 2-Me-benzyl 1317 Ph allyl 4-Me-benzyl 1318 Ph allyl 2-Cl-4-MeO-benzyl 1319 Ph allyl 2-MeO-benzyl 1320 Ph allyl 4-MeO-benzyl 1321 Ph 2-propynyl Me 1322 Ph 2-propynyl allyl 1323 Ph 2-propynyl benzyl 1324 Ph 2-propynyl 2-Cl-benzy 1325 Ph 2-propynyl 4-Cl-benzyl

TABLE 54 No R¹ R² R³ 1326 Ph 2-propynyl 2-Me-benzyl 1327 Ph 2-propynyl 4-Me-benzyl 1328 Ph 2-propynyl 2-Cl-4-MeO-benzyl 1329 Ph 2-propynyl 2-MeO-benzyl 1330 Ph 2-propynyl 4-MeO-benzyl 1331 Ph benzyl Me 1332 Ph benzyl allyl 1333 Ph benzyl benzyl 1334 Ph benzyl 2-Cl-benzyl 1335 Ph benzyl 4-Cl-benzyl 1336 Ph benzyl 2-Me-benzyl 1337 Ph benzyl 4-Me-benzyl 1338 Ph benzyl 2-Cl-4-MeO-benzyl 1339 Ph benzyl 2-MeO-benzyl 1340 Ph benzyl 4-MeO-benzyl 1341 Ph 4-Me-benzyl Me 1342 Ph 4-Me-benzyl allyl 1343 Ph 4-Me-benzyl benzyl 1344 Ph 4-Me-benzyl 2-Cl-benzyl 1345 Ph 4-Me-benzyl 4-Cl-benzyl 1346 Ph 4-Me-benzyl 2-Me-benzyl 1347 Ph 4-Me-benzyl 4-Me-benzyl 1348 Ph 4-Me-benzyl 2-Cl-4-MeO-benzyl 1349 Ph 4-Me-benzyl 2-MeO-benzyl 1350 Ph 4-Me-benzyl 4-MeO-benzyl

TABLE 55 No R¹ R² R³ 1351 Ph 4-Cl-benzyl Me 1352 Ph 4-Cl-benzyl allyl 1353 Ph 4-Cl-benzyl benzyl 1354 Ph 4-Cl-benzyl 2-Cl-benzyl 1355 Ph 4-Cl-benzyl 4-Cl-benzyl 1356 Ph 4-Cl-benzyl 2-Me-benzyl 1357 Ph 4-Cl-benzyl 4-Me-benzyl 1358 Ph 4-Cl-benzyl 2-Cl-4-MeO-benzyl 1359 Ph 4-Cl-benzyl 2-MeO-benzyl 1360 Ph 4-Cl-benzyl 4-MeO-benzyl 1361 Ph 4-MeO-benzyl Me 1362 Ph 4-MeO-benzyl allyl 1363 Ph 4-MeO-benzyl benzyl 1364 Ph 4-MeO-benzyl 2-Cl-benzyl 1365 Ph 4-MeO-benzyl 4-Cl-benzyl 1366 Ph 4-MeO-benzyl 2-Me-benzyl 1367 Ph 4-MeO-benzyl 4-Me-benzyl 1368 Ph 4-MeO-benzyl 2-Cl-4-MeO-benzyl 1369 Ph 4-MeO-benzyl 2-MeO-benzyl 1370 Ph 4-MeO-benzyl 4-MeO-benzyl 1371 Ph 2-pyridylCH₂ Me 1372 Ph 2-pyridylCH₂ allyl 1373 Ph 2-pyridylCH₂ benzyl 1374 Ph 2-pyridylCH₂ 2-Cl-benzyl 1375 Ph 2-pyridylCH₂ 4-Cl-benzyl

TABLE 56 No R¹ R² R³ 1376 Ph 2-pyridylCH₂ 2-Me-benzyl 1377 Ph 2-pyridylCH₂ 4-Me-benzyl 1378 Ph 2-pyridylCH₂ 2-Cl-4-MeO-benzyl 1379 Ph 2-pyridylCH₂ 2-MeO-benzyl 1380 Ph 2-pyridylCH₂ 4-MeO-benzyl 1381 Ph 3-pyridylCH₂ Me 1382 Ph 3-pyridylCH₂ allyl 1383 Ph 3-pyridylCH₂ benzyl 1384 Ph 3-pyridylCH₂ 2-Cl-benzyl 1385 Ph 3-pyridylCH₂ 4-Cl-benzyl 1386 Ph 3-pyridylCH₂ 2-Me-benzyl 1387 Ph 3-pyridylCH₂ 4-Me-benzyl 1388 Ph 3-pyridylCH₂ 2-Cl-4-MeO-benzyl 1389 Ph 3-pyridylCH₂ 2-MeO-benzyl 1390 Ph 3-pyridylCH₂ 4-MeO-benzyl 1391 Ph 4-pyridylCH₂ Me 1392 Ph 4-pyridylCH₂ allyl 1393 Ph 4-pyridylCH₂ benzyl 1394 Ph 4-pyridylCH₂ 2-Cl-benzyl 1395 Ph 4-pyridylCH₂ 4-Cl-benzyl 1396 Ph 4-pyridylCH₂ 2-Me-benzyl 1397 Ph 4-pyridylCH₂ 4-Me-benzyl 1398 Ph 4-pyridylCH₂ 2-Cl-4-MeO-benzyl 1399 Ph 4-pyridylCH₂ 2-MeO-benzyl 1400 Ph 4-pyridylCH₂ 4-MeO-benzyl

TABLE 57 No R¹ R² R³ 1401 Pr′ benzyl benzyl 1402 Pr′ benzyl 4-Cl-benzyl 1403 Pr′ benzyl 4-Me-benzyl 1404 Pr′ benzyl 4-MeO-benzyl 1405 Pr′ 4-Cl-benzyl benzyl 1406 Pr′ 4-Cl-benzyl 4-Cl-benzyl 1407 Pr′ 4-Cl-benzyl 4-Me-benzyl 1408 Pr′ 4-Cl-benzyl 4-MeO-benzyl 1409 Pr′ 4-Me-benzyl benzyl 1410 Pr′ 4-Me-benzyl 4-Cl-benzyl 1411 Pr′ 4-Me-benzyl 4-Me-benzyl 1412 Pr′ 4-Me-benzyl 4-MeO-benzyl 1413 Pr′ 4-MeO-benzyl benzyl 1414 Pr′ 4-MeO-benzyl 4-Cl-benzyl 1415 Pr′ 4-MeO-benzyl 4-Me-benzyl 1416 Pr′ 4-MeO-benzyl 4-MeO-benzyl 1417 Pr′ 4-pyridylCH₂ benzyl 1418 Pr′ 4-pyridylCH₂ 4-Cl-benzyl 1419 Pr′ 4-pyridylCH₂ 4-Me-benzyl 1420 Pr′ 4-pyridylCH₂ 4-MeO-benzyl 1421 Me benzyl Ph 1422 Me 4-Cl-benzyl Ph 1423 Me 4-Me-benzyl Ph 1424 Me 4-MeO-benzyl Ph 1425 Me 4-pyridylCH₂ Ph

TABLE 58 No R¹ R² R³ 1426 Me benzyl 3-Cl-Ph 1427 Me 4-Cl-benzyl 3-Cl-Ph 1428 Me 4-Me-benzyl 3-Cl-Ph 1429 Me 4-MeO-benzyl 3-Cl-Ph 1430 Me 4-pyridylCH₂ 3-Cl-Ph 1431 Me benzyl 4-Cl-Ph 1432 Me 4-Cl-benzyl 4-Cl-Ph 1433 Me 4-Me-benzyl 4-Cl-Ph 1434 Me 4-MeO-benzyl 4-Cl-Ph 1435 Me 4-pyridylCH₂ 4-Cl-Ph 1436 Me benzyl 3-Me-Ph 1437 Me 4-Cl-benzyl 3-Me-Ph 1438 Me 4-Me-benzyl 3-Me-Ph 1439 Me 4-MeO-benzyl 3-Me-Ph 1440 Me 4-pyridylCH₂ 3-Me-Ph 1441 Me benzyl 4-Me-Ph 1442 Me 4-Cl-benzyl 4-Me-Ph 1443 Me 4-Me-benzyl 4-Me-Ph 1444 Me 4-MeO-benzyl 4-Me-Ph 1445 Me 4-pyridylCH₂ 4-Me-Ph 1446 Me benzyl 3-MeO-Ph 1447 Me 4-Cl-benzyl 3-MeO-Ph 1448 Me 4-Me-benzyl 3-MeO-Ph 1449 Me 4-MeO-benzyl 3-MeO-Ph 1450 Me 4-pyridylCH₂ 3-MeO-Ph

TABLE 59 No R¹ R² R³ 1451 Me benzyl 4-MeO-Ph 1452 Me 4-Cl-benzyl 4-MeO-Ph 1453 Me 4-Me-benzyl 4-MeO-Ph 1454 Me 4-MeO-benzyl 4-MeO-Ph 1455 Me 4-pyridylCH₂ 4-MeO-Ph 1456 Et benzyl Ph 1457 Et 4-Cl-benzyl Ph 1458 Et 4-Me-benzyl Ph 1459 Et 4-MeO-benzyl Ph 1460 Et 4-pyridylCH₂ Ph 1461 Et benzyl 3-Cl-Ph 1462 Et 4-Cl-benzyl 3-Cl-Ph 1463 Et 4-Me-benzyl 3-Cl-Ph 1464 Et 4-MeO-benzyl 3-Cl-Ph 1465 Et 4-pyridylCH₂ 3-Cl-Ph 1466 Et benzyl 4-Cl-Ph 1467 Et 4-Cl-benzyl 4-Cl-Ph 1468 Et 4-Me-benzyl 4-Cl-Ph 1469 Et 4-MeO-benzyl 4-Cl-Ph 1470 Et 4-pyridylCH₂ 4-Cl-Ph 1471 Et benzyl 3-Me-Ph 1472 Et 4-Cl-benzyl 3-Me-Ph 1473 Et 4-Me-benzyl 3-Me-Ph 1474 Et 4-MeO-benzyl 3-Me-Ph 1475 Et 4-pyridylCH₂ 3-Me-Ph

TABLE 60 No R¹ R² R³ 1476 Et benzyl 4-Me-Ph 1477 Et 4-Cl-benzyl 4-Me-Ph 1478 Et 4-Me-benzyl 4-Me-Ph 1479 Et 4-MeO-benzyl 4-Me-Ph 1480 Et 4-pyridylCH₂ 4-Me-Ph 1481 Et benzyl 3-MeO-Ph 1482 Et 4-Cl-benzyl 3-MeO-Ph 1483 Et 4-Me-benzyl 3-MeO-Ph 1484 Et 4-MeO-benzyl 3-MeO-Ph 1485 Et 4-pyridylCH₂ 3-MeO-Ph 1486 Et benzyl 4-MeO-Ph 1487 Et 4-Cl-benzyl 4-MeO-Ph 1488 Et 4-Me-benzyl 4-MeO-Ph 1489 Et 4-MeO-benzyl 4-MeO-Ph 1490 Et 4-pyridylCH₂ 4-MeO-Ph 1491 Me 4-H₂N-benzyl benzyl 1492 Me 4-H₂N-benzyl 4-Cl-benzyl 1493 Me 4-H₂N-benzyl 4-HO-benzyl 1494 Me 4-H₂N-benzyl 4-MeO-benzyl 1495 Me 4-H₂N-benzyl α-Me-4-MeO-benzyl 1496 Me 4-H₂N-benzyl 4-EtO-benzyl 1497 Me 4-H₂N-benzyl 4-PrO-benzyl 1498 Me 4-H₂N-benzyl 4-AcO-benzyl 1499 Me 4-H₂N-benzyl 4-MOMO-benzyl 1500 Me 4-H₂N-benzyl 4-MeO-Ph(CH₂)₂

TABLE 61 No R¹ R² R³ 1501 Me 4-AcNH-benzyl benzyl 1502 Me 4-AcNH-benzyl 4-Cl-benzyl 1503 Me 4-AcNH-benzyl 4-HO-benzyl 1504 Me 4-AcNH-benzyl 4-MeO-benzyl 1505 Me 4-AcNH-benzyl α-Me-4-MeO-benzyl 1506 Me 4-AcNH-benzyl 4-EtO-benzyl 1507 Me 4-AcNH-benzyl 4-PrO-benzyl 1508 Me 4-AcNH-benzyl 4-AcO-benzyl 1509 Me 4-AcNH-benzyl 4-MOMO-benzyl 1510 Me 4-AcNH-benzyl 4-MeO-Ph(CH₂)₂ 1511 Me 4-CF₃-benzyl benzyl 1512 Me 4-CF₃-benzyl 4-Cl-benzyl 1513 Me 4-CF₃-benzyl 4-HO-benzyl 1514 Me 4-CF₃-benzyl 4-MeO-benzyl 1515 Me 4-CF₃-benzyl α-Me-4-MeO-benzyl 1516 Me 4-CF₃-benzyl 4-EtO-benzyl 1517 Me 4-CF₃-benzyl 4-PrO-benzyl 1518 Me 4-CF₃-benzyl 4-AcO-benzyl 1519 Me 4-CF₃-benzyl 4-MOMO-benzyl 1520 Me 4-CF₃-benzyl 4-MeO-Ph(CH₂)₂ 1521 Me 2,5-(Me)₂-benzyl benzyl 1522 Me 2,5-(Me)₂-benzyl 4-Cl-benzyl 1523 Me 2,5-(Me)₂-benzyl 4-HO-benzyl 1524 Me 2,5-(Me)₂-benzyl 4-MeO-benzyl 1525 Me 2,5-(Me)₂-benzyl α-Me-4-MeO-benzyl

TABLE 62 No R¹ R² R³ 1526 Me 2,5-(Me)₂-benzyl 4-EtO-benzyl 1527 Me 2,5-(Me)₂-benzyl 4-PrO-benzyl 1528 Me 2,5-(Me)₂-benzyl 4-AcO-benzyl 1529 Me 2,5-(Me)₂-benzyl 4-MOMO-benzyl 1530 Me 2,5-(Me)₂-benzyl 4-MeO-Ph(CH₂)₂ 1531 Me 1-naphthylmethyl benzyl 1532 Me 1-naphthylmethyl 4-Cl-benzyl 1533 Me 1-naphthylmethyl 4-HO-benzyl 1534 Me 1-naphthylmethyl 4-MeO-benzyl 1535 Me 1-naphthylmethyl α-Me-4-MeO-benzyl 1536 Me 1-naphthylmethyl 4-EtO-benzyl 1537 Me 1-naphthylmethyl 4-PrO-benzyl 1538 Me 1-naphthylmethyl 4-AcO-benzyl 1539 Me 1-naphthylmethyl 4-MOMO-benzyl 1540 Me 1-naphthylmethyl 4-MeO-Ph(CH₂)₂ 1541 Me 2-naphthylmethyl benzyl 1542 Me 2-naphthylmethyl 4-Cl-benzyl 1543 Me 2-naphthylmethyl 4-HO-benzyl 1544 Me 2-naphthylmethyl 4-MeO-benzyl 1545 Me 2-naphthylmethyl α-Me-4-MeO-benzyl 1546 Me 2-naphthylmethyl 4-EtO-benzyl 1547 Me 2-naphthylmethyl 4-PrO-benzyl 1548 Me 2-naphthylmethyl 4-AcO-benzyl 1549 Me 2-naphthylmethyl 4-MOMO-benzyl 1550 Me 2-naphthylmethyl 4-MeO-Ph(CH₂)₂

TABLE 63 No R¹ R² R³ 1551 Me 2-thenyl benzyl 1552 Me 2-thenyl 4-Cl-benzyl 1553 Me 2-thenyl 4-HO-benzyl 1554 Me 2-thenyl 4-MeO-benzyl 1555 Me 2-thenyl α-Me-4-MeO-benzyl 1556 Me 2-thenyl 4-EtO-benzyl 1557 Me 2-thenyl 4-PrO-benzyl 1558 Me 2-thenyl 4-AcO-benzyl 1559 Me 2-thenyl 4-MOMO-benzyl 1560 Me 2-thenyl 4-MeO-Ph(CH₂)₂ 1561 Me 3-thenyl benzyl 1562 Me 3-thenyl 4-Cl-benzyl 1563 Me 3-thenyl 4-HO-benzyl 1564 Me 3-thenyl 4-MeO-benzyl 1565 Me 3-thenyl α-Me-4-MeO-benzyl 1566 Me 3-thenyl 4-EtO-benzyl 1567 Me 3-thenyl 4-PrO-benzyl 1568 Me 3-thenyl 4-AcO-benzyl 1569 Me 3-thenyl 4-MOMO-benzyl 1570 Me 3-thenyl 4-MeO-Ph(CH₂)₂ 1571 Me benzyl 4-HO-benzyl 1572 Me benzyl 4-EtO-benzyl 1573 Me benzyl 4-PrO-benzyl 1574 Me benzyl 4-AcO-benzyl 1575 Me benzyl 4-MOMO-benzyl

TABLE 64 No R¹ R² R³ 1576 Me benzyl 4-MeO-Ph(CH₂)₂ 1577 Me benzyl 4-AllylO-benzyl 1578 Me benzyl 4-PhO-benzyl 1579 Me 2-propynyl 4-HO-benzyl 1580 Me 2-propynyl 4-EtO-benzyl 1581 Me 2-propynyl 4-PrO-benzyl 1582 Me 2-propynyl 4-AcO-benzyl 1583 Me 2-propynyl 4-MOMO-benzyl 1584 Me 2-propynyl 4-MeO-Ph(CH₂)₂ 1585 Me 2-Cl-benzyl 4-HO-benzyl 1586 Me 2-Cl-benzyl 4-EtO-benzyl 1587 Me 2-Cl-benzyl 4-PrO-benzyl 1588 Me 2-Cl-benzyl 4-AcO-benzyl 1589 Me 2-Cl-benzyl 4-MOMO-benzyl 1590 Me 2-Cl-benzyl 4-MeO-Ph(CH₂)₂ 1591 Me 4-Cl-benzyl 4-HO-benzyl 1592 Me 4-Cl-benzyl 4-EtO-benzyl 1593 Me 4-Cl-benzyl 4-PrO-benzyl 1594 Me 4-Cl-benzyl 4-AcO-benzyl 1595 Me 4-Cl-benzyl 4-MOMO-benzyl 1597 Me 2-MeO-benzyl 4-HO-benzyl 1598 Me 2-MeO-benzyl 4-EtO-benzyl 1599 Me 2-MeO-benzyl 4-PrO-benzyl 1600 Me 2-MeO-benzyl 4-AcO-benzyl

TABLE 65 No R¹ R² R³ 1601 Me 2-MeO-benzyl 4-MOMO-benzyl 1602 Me 2-MeO-benzyl 4-MeO-Ph(CH₂)₂ 1603 Me 4-MeO-benzyl 4-HO-benzyl 1604 Me 4-MeO-benzyl 4-EtO-benzyl 1605 Me 4-MeO-benzyl 4-Pr-benzyl 1606 Me 4-MeO-benzyl 4-AcO-benzyl 1607 Me 4-MeO-benzyl 4-MOMO-benzyl 1608 Me 4-MeO-benzyl 4-MeO-Ph(CH₂)₂ 1609 Me 2-pyridylCH₂ 4-HO-benzyl 1610 Me 2-pyridylCH₂ 4-EtO-benzyl 1611 Me 2-pyridylCH₂ 4-PrO-benzyl 1612 Me 2-pyridylCH₂ 4-AcO-benzyl 1613 Me 2-pyridylCH₂ 4-MOMO-benzyl 1614 Me 2-pyridylCH₂ 4-MeO-Ph(CH₂)₂ 1615 Me 4-pyridylCH₂ 4-HO-benzyl 1616 Me 4-pyridylCH₂ 4-EtO-benzyl 1617 Me 4-pyridylCH₂ 4-PrO-benzyl 1618 Me 4-pyridylCH₂ 4-AcO-benzyl 1619 Me 4-pyridylCH₂ 4-MOMO-benzyl 1620 Me 4-pyridylCH₂ 4-MeO-Ph(CH₂)₂ 1621 Et 4-H₂N-benzyl benzyl 1622 Et 4-H₂N-benzyl 4-Cl-benzyl 1623 Et 4-H₂N-benzyl 4-HO-benzyl 1624 Et 4-H₂N-benzyl 4-MeO-benzyl 1625 Et 4-H₂N-benzyl α-Me-4-MeO-benzyl

TABLE 66 No R¹ R² R³ 1626 Et 4-H₂N-benzyl 4-EtO-benzyl 1627 Et 4-H₂N-benzyl 4-PrO-benzyl 1628 Et 4-H₂N-benzyl 4-AcO-benzyl 1629 Et 4-H₂N-benzyl 4-MOMO-benzyl 1630 Et 4-H₂N-benzyl 4-MeO-Ph(CH₂)₂ 1631 Et 4-AcNH-benzyl benzyl 1632 Et 4-ACNH-benzyl 4-Cl-benzyl 1633 Et 4-AcNH-benzyl 4-HO-benzyl 1634 Et 4-AcNH-benzyl 4-MeO-benzyl 1635 Et 4-AcNH-benzyl α-Me-4-MeO-benzyl 1636 Et 4-AcNH-benzyl 4-EtO-benzyl 1637 Et 4-AcNH-benzyl 4-PrO-benzyl 1638 Et 4-AcNH-benzyl 4-AcO-benzyl 1639 Et 4-AcNH-benzyl 4-MOMO-benzyl 1640 Et 4-AcNH-benzyl 4-MeO-Ph(CH₂)₂ 1641 Et 4-CF₃-benzyl benzyl 1642 Et 4-CF₃-benzyl 4-Cl-benzyl 1643 Et 4-CF₃-benzyl 4-HO-benzyl 1644 Et 4-CF₃-benzyl 4-MeO-benzyl 1645 Et 4-CF₃-benzyl α-Me-4-MeO-benzyl 1646 Et 4-CF₃-benzyl 4-EtO-benzyl 1647 Et 4-CF₃-benzyl 4-PrO-benzyl 1648 Et 4-CF₃-benzyl 4-AcO-benzyl 1649 Et 4-CF₃-benzyl 4-MOMO-benzyl 1650 Et 4-CF₃-benzyl 4-MeO-Ph(CH₂)₂

TABLE 67 No R¹ R² R³ 1651 Et 2,5-(Me)₂-benzyl benzyl 1652 Et 2,5-(Me)₂-benzyl 4-Cl-benzyl 1653 Et 2,5-(Me)₂-benzyl 4-HO-benzyl 1654 Et 2,5-(Me)₂-benzyl 4-MeO-benzyl 1655 Et 2,5-(Me)₂-benzyl α-Me-4-MeO-benzyl 1656 Et 2,5-(Me)₂-benzyl 4-EtO-benzyl 1657 Et 2,5-(Me)₂-benzyl 4-PrO-benzyl 1658 Et 2,5-(Me)₂-benzyl 4-AcO-benzyl 1659 Et 2,5-(Me)₂-benzyl 4-MOMO-benzyl 1660 Et 2,5-(Me)₂-benzyl 4-MeO-Ph(CH₂)₂ 1661 Et 1-naphthylmethyl benzyl 1662 Et 1-naphthylmethyl 4-Cl-benzyl 1663 Et 1-naphthylmethyl 4-HO-benzyl 1664 Et 1-naphthylmethyl 4-MeO-benzyl 1665 Et 1-naphthylmethyl α-Me-4-MeO-benzyl 1666 Et 1-naphthylmethyl 4-EtO-benzyl 1667 Et 1-naphthylmethyl 4-PrO-benzyl 1668 Et 1-naphthylmethyl 4-AcO-benzyl 1669 Et 1-naphthylmethyl 4-MOMO-benzyl 1670 Et 1-naphthylmethyl 4-MeO-Ph(CH₂)₂ 1671 Et 2-naphthylmethyl benzyl 1672 Et 2-naphthylmethyl 4-Cl-benzyl 1673 Et 2-naphthylmethyl 4-HO-benzyl 1674 Et 2-naphthylmethyl 4-MeO-benzyl 1675 Et 2-naphthylmethyl α-Me-4-MeO-benzyl

TABLE 68 No R¹ R² R³ 1676 Et 2-naphthylmethyl 4-EtO-benzyl 1677 Et 2-naphthylmethyl 4-PrO-benzyl 1678 Et 2-naphthylmethyl 4-AcO-benzyl 1679 Et 2-naphthylmethyl 4-MOMO-benzyl 1680 Et 2-naphthylmethyl 4-MeO-Ph(CH₂)₂ 1681 Et 2-thenyl benzyl 1682 Et 2-thenyl 4-Cl-benzyl 1683 Et 2-thenyl 4-HO-benzyl 1684 Et 2-thenyl 4-MeO-benzyl 1685 Et 2-thenyl α-Me-4-MeO-benzyl 1686 Et 2-thenyl 4-EtO-benzyl 1687 Et 2-thenyl 4-PrO-benzyl 1688 Et 2-thenyl 4-AcO-benzyl 1689 Et 2-thenyl 4-MOMO-benzyl 1690 Et 2-thenyl 4-MeO-Ph(CH₂)₂ 1691 Et 3-thenyl benzyl 1692 Et 3-thenyl 4-Cl-benzyl 1693 Et 3-thenyl 4-HO-benzyl 1694 Et 3-thenyl 4-MeO-benzyl 1695 Et 3-thenyl α-Me-4-MeO-benzyl 1696 Et 3-thenyl 4-EtO-benzyl 1697 Et 3-thenyl 4-PrO-benzyl 1698 Et 3-thenyl 4-AcO-benzyl 1699 Et 3-thenyl 4-MOMO-benzyl 1700 Et 3-thenyl 4-MeO-Ph(CH₂)₂

TABLE 69 No R¹ R² R³ 1701 Et benzyl 4-HO-benzyl 1702 Et benzyl 4-EtO-benzyl 1703 Et benzyl 4-PrO-benzyl 1704 Et benzyl 4-AcO-benzyl 1705 Et benzyl 4-MOMO-benzyl 1706 Et benzyl 4-MeO-Ph(CH₂)₂ 1707 Et benzyl 4-AllylO-benzyl 1708 Et benzyl 4-PhO-benzyl 1709 Et 2-propynyl 4-HO-benzyl 1710 Et 2-propynyl 4-EtO-benzyl 1711 Et 2-propynyl 4-PrO-benzyl 1712 Et 2-propynyl 4-AcO-benzyl 1713 Et 2-propynyl 4-MOMO-benzyl 1714 Et 2-propynyl 4-MeO-Ph(CH₂)₂ 1715 Et 2-Cl-benzyl 4-HO-benzyl 1716 Et 2-Cl-benzyl 4-EtO-benzyl 1717 Et 2-Cl-benzyl 4-PrO-benzyl 1718 Et 2-Cl-benzyl 4-AcO-benzyl 1719 Et 2-Cl-benzyl 4-MOMO-benzyl 1720 Et 2-Cl-benzyl 4-MeO-Ph(CH₂)₂ 1721 Et 4-Cl-benzyl 4-HO-benzyl 1722 Et 4-Cl-benzyl 4-EtO-benzyl 1723 Et 4-Cl-benzyl 4-PrO-benzyl 1724 Et 4-Cl-benzyl 4-AcO-benzyl 1725 Et 4-Cl-benzyl 4-MOMO-benzyl

TABLE 70 No R¹ R² R³ 1726 Et 4-Cl-benzyl 4-MeO-Ph(CH₂)₂ 1727 Et 2-MeO-benzyl 4-HO-benzyl 1728 Et 2-MeO-benzyl 4-EtO-benzyl 1729 Et 2-MeO-benzyl 4-PrO-benzyl 1730 Et 2-MeO-benzyl 4-AcO-benzyl 1731 Et 2-MeO-benzyl 4-MOMO-benzyl 1732 Et 2-MeO-benzyl 4-MeO-Ph(CH₂)₂ 1733 Et 4-MeO-benzyl 4-HO-benzyl 1734 Et 4-MeO-benzyl 4-EtO-benzyl 1735 Et 4-MeO-benzyl 4-PrO-benzyl 1736 Et 4-MeO-benzyl 4-AcO-benzyl 1737 Et 4-MeO-benzyl 4-MOMO-benzyl 1738 Et 4-MeO-benzyl 4-MeO-Ph(CH₂)₂ 1739 Et 2-pyridylCH₂ 4-HO-benzyl 1740 Et 2-pyridylCH₂ 4-EtO-benzyl 1741 Et 2-pyridylCH₂ 4-PrO-benzyl 1742 Et 2-pyridylCH₂ 4-AcO-benzyl 1743 Et 2-pyridylCH₂ 4-MOMO-benzyl 1744 Et 2-pyridylCH₂ 4-MeO-Ph(CH₂)₂ 1745 Et 4-pyridylCH₂ 4-HO-benzyl 1746 Et 4-pyridylCH₂ 4-EtO-benzyl 1747 Et 4-pyridylCH₂ 4-PrO-benzyl 1748 Et 4-pyridylCH₂ 4-AcO-benzyl 1749 Et 4-pyridylCH₂ 4-MOMO-benzyl 1750 Et 4-pyridylCH₂ 4-MeO-Ph(CH₂)₂

TABLE 71 No Physical Data A-176 mp 89-97° C. A-1301 mp 83-92° C. A-1310 Isomer A: mp 84-86° C. Isomer B: mp 173-174° C. B-476 mp 112-114° C. B-480 mp 78-89° C. B-1301 ¹H-NMR(CDCl₃) δ ppm: 2.97(3H, d, J=4.9), 3.91(3H, s), 3.94 (3H, s), 5.90(1H, br), 7.40(5H, m) B-1310 mp 136-137° C. B-1331 ¹H-NMR(CDCl₃) δ ppm: 2.89(3H, d, J=4.9), 3.91(3H, s), 5.25 (1H, s), 6.58(1H, br), 7.25-7.40(8H, m), 7.51-7.55(2H, m) C-1 ¹H-NMR(CDCl₃) δ ppm: 2.04(3H, s), 2.85(3H, s), 3.03(3H, s), 3.93(3H, s), 3.97(3H, s) C-10 ¹H-NMR(CDCl₃) δ ppm: 2.02(3H, s), 2.74(3H, s), 3.00(3H, s), 3.92(3H, s), 5.19(2H, s), 7.33(5H, m) C-11 ¹H-NMR(CDCl₃) δ ppm: 2.01(3H, s), 2.80(3H, s), 3.03(3H, s), 3.93(3H, s), 5.30(1H, d, J=13.4), 5.33(1H, d, J=13.4), 7.20- 7.43(4H, m) C-12 ¹H-NMR(CDCl₃) δ ppm: 2.04(3H, s), 2.77(3H, s), 3.03(3H, s), 3.92(3H, s), 5.16(2H, s), 7.20-7.32(4H, m) C-13 mp 83-85° C. C-19 ¹H-NMR(CDCl₃) δ ppm: 2.02(3H, s), 2.71(3H, s), 2.99(3H, s), 3.80(3H, s), 3.91(3H, s), 5.11(2H, s), 6.86(2H, d, J=8.5), 7.27 (2H, d, J=8.5) C-20 ¹H-NMR(CDCl₃) δ ppm: 1.99(3H, s), 2.75(3H, s), 2.99(3H, s), 3.92(3H, s), 5.30(2H, s), 6.86-7.47(9H, m) C-21 ¹H-NMR(CDCl₃) δ ppm: 2.00(3H, s), 2.79(3H, s), 3.03(3H, s), 3.93(3H, s), 5.12(2H, s), 7.18(1H, dd, J=8.5, 1.8), 7.43(2H, m) C-86 ¹H-NMR(CDCl₃) δ ppm: 2.04(3H, s), 2.78(3H, s), 3.01(3H, s), 4.62(2H, d, J=5.5), 5.15-5.38(4H, m), 5.87-6.02(1H, m), 7.20- 7.47(4H, m)

TABLE 72 No Physical Data C-87 ¹H-NMR(CDCl₃) δ ppm: 2.04(3H, s), 2.76(3H, s), 3.01(3H, s), 4.61(2H, d, J=5.5), 5.16(2H, s), 5.16-5.29(2H, m), 5.87-6.02 (1H, m), 7.20-7.32(4H, m) C-94 ¹H-NMR(CDCl₃) δ ppm: 2.05(3H, s), 2.70(3H, s), 2.98(3H, s), 3.80(3H, s), 4.61(2H, d, J=5.5), 5.12(2H, s), 5.16-5.28(2H, m), 5.87-6.01(1 H, m), 6.86(2H, d, J=8.5), 7.28(2H, d, J=8.5) C-95 ¹H-NMR(CDCl₃) δ ppm: 2.02(3H, s), 2.73(3H, s), 2.98(3H, s), 4.61(2H, d, J=5.5), 5.16-5.29(2H, m), 5.30(2H, s), 5.87-6.02 (1H, m), 6.87-7.47(9H, m) C-96 ¹H-NMR(CDCl₃) δ ppm: 2.03(3H, s), 2.77(3H, s), 3.01(3H, s), 4.62(2H, d, J=5.5), 5.12(2H, s), 5.12-5.29(2H, m), 5.87-6.02 (1H, m), 7.18(1H, dd, J=8.5, 1.8), 7.26-7.43(2H, m) C-101 ¹H-NMR(CDCl₃) δ ppm 2.09(3H, s), 2.79(3H, s), 2.98(3H, s), 3.97(3H, s), 4.74-4.84(2H, m), 6.27-6.37(1H, m), 6.57-6.63 (1H, m), 7.21-7.46(5H, m) C-144 mp 96-99° C. C-146 mp 82-83.5° C. C-176 ¹H-NMR(CDCl₃) δ ppm: 2.06(3H, s), 2.63(3H, s), 2.98(3H, s), 3.95(3H, s), 5.12(1H, d, J=12.2), 5.15(1H, d, J=12.2), 7.32(5H, m) C-180 ¹H-NMR(CDCl₃) δ ppm: 2.06(3H, s), 2.64(3H, s), 2.99(3H, s), 4.64(2H, d, J=5.9), 5.13-5.32(4H, m), 5.88-6.03(1H, m), 7.37 (5H, m) C-185 mp 102-104° C. C-194 ¹H-NMR(CDCl₃) δ ppm: 2.04(3H, s), 2.50(3H, s), 2.95(3H, s), 3.80(3H, s), 5.09 and 5.15(each 1H, ABq, J=12.2), 5.10(2H, s), 6.84(2H, d, J=8.7), 7.26(2H, d, J=8.8), 7.31(5H, m) C-219 mp 93-93.5° C. C-251 mp 82.5-83.5° C. C-276 mp 49.5-51° C. C-301 mp 92-93° C. C-326 mp 54.5-56° C. C-376 mp 68-69° C.

TABLE 73 No Physical Data C-451 mp 93-94° C. C-476 mp 77-79° C. C-480 ¹H-NMR(CDCl₃) δ ppm: 2.06(3H, s), 2.70(3H, s), 3.01(3H, s), 4.65(2H, m), 5.07(2H, s), 5.19-5.32(2H, m), 5.88-6.03(1H, m), 7.16(1H, dd, J=8.5, 1.8), 7.40-7.44(2H, m) C-619 ¹H-NMR(CDCl₃) δ ppm: 1.05(3H, t, J=7.3), 2.50-2.63(2H, m), 2.68(3H, s), 2.98(3H, s), 3.80(3H, s), 3.89(3H, s), 5.11(2H, s), 6.86(2H, d, J=9.2), 7.28(2H, d, J=9.2) C-780 ¹H-NMR(CDCl₃) δ ppm: 1.08(3H, t, J=7.3), 2.53-2.66(2H, m), 2.60(3H, s), 2.97(3H, s), 4.64(2H, d, J=6.1), 5.12(1H, d, J=11.6), 5.14(1H, d, J=11.6), 5.18-5.31(2H, m), 5.88-6.02 (1H, m), 7.33(5H, m) C-1310 mp 111-113° C. C-1331 mp 78-96° C. F-176 ¹H-NMR(CDCl₃) δ ppm: 2.08(3H, s), 3.23(3H, s), 3.44(3H, s), 3.97(3H, s), 5.16(2H, s), 7.26-7.34(5H, m) F-180 ¹H-NMR(CDCl₃) δ ppm: 2.07(3H, s), 3.23(3H, s), 3.45(3H, s), 4.66(2H, d, J=5.5), 5.16(2H, s), 5.16-5.33(2H, m), 5.92-6.02 (1H, m), 7.26-7.32(5H, m) G-194 ¹H-NMR(CDCl₃) δ ppm: 1.59-1.82(4H, m), 2.03(3H, m), 2.84 (2H, m), 3.49(2H, m), 3.79(3H, s), 5.10-5.13(4H, m), 6.84 (2H, d, J=8.8), 7.25(2H, d, J=8.8), 7.30(5H, m) H-176 mp 121-123° C. H-194 ¹H-NMR(CDCl₃) δ ppm: 1.10-1.28(2H, m), 1.47(4H, m), 2.05 (3H, s), 2.80-2.96(2H, m), 3.45(1H, m), 3.64(1H, m), 3.80 (3H, s), 5.09(2H, s), 5.10 and 5.16(each 1H, ABq, J=12.2), 6.84 (2H, d, J=8.5), 7.25(2H, d, J=8.5), 7.31(5H, m) L-794 ¹H-NMR(CDCl₃) δ ppm: 0.46-1.01(2H, m), 1.08 and 1.12(total 3H, t, J=7.6), 1.36-1.90(2H, m), 1.92 and 1.95(total 3H, s), 2.51-2.81(4H, m), 3.07(1H, m), 3.75(1H, m), 3.80(3H, s), 4.46(1H, m), 4.79 and 4.92(total 1H, br d), 5.05-5.25(4H, m), 6.83-6.89(2H, m), 7.27-7.36(7H, m)

TABLE 74 No Physical Data M-1194 ¹H-NMR(CDCl₃) δ ppm: 023-1.10(2H, m), 1.11 and 1.12(total 3H, t, J=7.6), 1.41-1.83(2H, m), 1.92 and 2.03(total 3H, s), 2.57-2.74(4H, m), 2.95 and 3.19(total 1H, m), 3.76(1H, m), 3.80 and 3.81(total 3H, s), 4.40(1H, m), 5.04-5.18(4H, m), 6.83-6.90(2H, m), 7.17-7.32(4H, m), 7.56-7.58(2H, m) N-794 mp 136-137° C. O-794 ¹H-NMR(CDCl₃) δ ppm: 0.51 and 0.96(total 1H, m), 1.08 and 1.11(total 3H, t, J=7.6), 1.37-1.56(1H, m), 1.81(1H, m), 2.50- 2.78(4H, m), 3.03(1H, m), 3.66 and 3.67(total 3H, s), 3.79 and 3.80(total 3H, s), 4.10-4.22(2H, m), 5.05-5.21(4H, m), 6.85 (2H, br d, J=8.8), 7.24-7.34(7H, m) P-794 ¹H-NMR(CDCl₃) δ ppm: 0.47-1.20(2H, m), 1.09 and 1.12(total 3H, t, J=7.6), 1.42-1.58(1H, m), 1.83(1H, m), 2.51-2.78(4H, m), 2.90 and 2.92(total 3H, s), 3.03-3.36(2H, m), 3.62-3.79 (1H, m), 3.80 and 3.81(total 3H, s), 4.40(1H, m), 5.05-5.22 (4H, m), 6.85 and 6.86(total 2H, d, J =8.5), 7.23-7.36(7H, m) R-194 ¹H-NMR(CDCl₃) δ ppm: 1.25-1.81(4H, m), 2.05 and 2.06(total 3H, s), 2.64-2.89(1H, m), 3.30 and 3.31(total 3H, s), 3.79 and 3.80(total 3H, s), 3.10-3.95(4H, m), 5.05-5.18(4H, m), 6.85 (2H, br d, J =8.5), 7.24-7.33(7H, m) T-794 ¹H-NMR(CDCl₃) δ ppm: 1.08(3H, t, J=7.3), 1.75-2.76(4H, m), 2.62(2H, q, J=7.3), 2.91-3.01(2H, m), 3.44-3.55(1H, m), 3.79 (3H, s), 3.80-3.96(1H, m), 5.05(1H, d, J=12.2), 5.10(2H, s), 5.16(1H, d, J=12.2), 6.85(2H, dd, J=1.2, 8.6), 7.12(1H, br), 7.28(7H, m) U-794 ¹H-NMR(CDCl₃) δ ppm: 1.08(3H, t, J=7.3), 1.78-2.68(4H, m), 2.61(2H, q, J=7.3), 2.89-3.01(2H, m), 3.43-3.53(1H, m), 3.79 (3H, s), 3.82 and 3.83(total 3H, s), 3.80-3.95(1 H, m), 5.05(1H, d, J=12.2), 5.09(2H, s), 5.15(1H, d, J=12.2), 6.84(2H, d, J=8.9), 7.27(7H, m) V-794 mp 92-93° C. W-10 ¹H-NMR(CDCl₃) δ ppm: 2.02(3H, s), 3.10-3.14(2H, m), 3.43- 3.58(2H, m), 3.62-3.75(4H, m), 3.93(3H, s), 5.20(2H, s), 7.34 (5H, m)

TABLE 75 No Physical Data W-144 ¹H-NMR(CDCl₃) δ ppm: 2.07(3H, s), 2.44(1H, t, J=2.5), 3.10 (2H, m), 3.46(1H, m), 3.57-3.78(5H, m), 3.81(3H, s), 4.72 (2H, d, J 2.5), 5.13(2H, s), 6.86(2H, d, J=8.7), 7.27(2H, d, J= 8.7) W-176 mp 111-113° C. W-194 ¹H-NMR(CDCl₃) δ ppm: 2.06(3H, s), 2.84(1H, ddd, J=3.2, 6.4, 13.4), 2.93(1H, ddd, J=3.2, 6.6, 13.4), 3.17(1H, ddd, J=3.2, 6.6, 11.5), 3.29(1H, ddd, 3.2, 6.4, 11.5), 3.57-3.62(4H. m), 3.80 (3H, s), 5.10(2H, s), 5.11 and 5.17(each 1H, ABq, J=12.2), 6.85 (2H, d, J=8.5), 7.25(2H, d, J=8.5), 7.31(5H, m) W-199 ¹H-NMR(CDCl₃) δ ppm: 2.01(3H, s), 2.91(1H, m), 3.13(1H, m), 3.29(1H, m), 3.52-3.72(5H, m), 3.88(3H, s), 5.13 and 5.22 (each 1H, ABq, J=12.2), 6.99(2H, d, J=9.0), 7.27-7.35(5H, m), 7.89(2H, d, J=9.0)) W-319 ¹H-NMR(CDCl₃) δ ppm: 2.06(3H, s), 2.85-3.03(2H, m), 3.21- 3.38(2H, m), 3.58-3.63(4H, m), 3.80(3H, s), 5.06 and 5.13 (each 1H, ABq, J=12.5), 5.11(2H, s), 6.86(2H, d, J=8.8), 7.22-7.33(6H, m) W-469 ¹H-NMR(CDCl₃) δ ppm: 2.03(3H, s), 2.86-3.01(2H, m), 3.23- 3.35(2H, m), 3.59-3.65(4H, m), 3.78(6H, s), 5.03 and 5.11 (each 1H, ABq, J=12.0), 5.09(2H, s), 6.85(2H, d, J=8.8), 6.86 (2H, d, J=8.8), 7.25(2H, d, J=8.8), 7.26(2H, d, J=8.8) W-569 ¹H-NMR(CDCl₃) δ ppm: 2.13(3H, s), 2.86-3.04(2H, m), 3.19- 3.37(2H, m), 3.52-3.63(4H, m), 3.80(3H, s), 5.12(2H, s), 5.12 and 5.29(each 1H, ABq, J=12.0), 6.86(2H, d, J=8.8), 7.18- 7.31(2H, m), 7.26(2H, d, J=8.8), 7.67(1H, dt, J=1.7, 7.6), 8.57(2H, br d, J=4.2) W-594 ¹H-NMR(CDCl₃) δ ppm: 2.06(3H, s), 2.91-2.99(2H, m), 3.10- 3.17(2H, m), 3.58-3.67(4H, m), 3.80(3H, s), 5.11(2H, s), 5.13 and 5.18(each 1H, ABq, J=12.5), 6.86(2H, d, J=8.5), 7.25 (2H, d, J=8.5), 7.26(1H, m), 7.63(1H, br d, J=7.8), 8.55-8.58 (2H, m) W-785 ¹H-NMR(CDCl₃) 8 ppm: 1.06(3H, t, J=7.2), 2.60(2H, q, J=7.2), 2.75-2.96(2H, m), 3.12-3.31(2H, m), 3.54-3.64(4H, m), 5.10 (1H, d, J=12.2), 5.18(1H, d, J=12.2), 7.32(10H, m)

TABLE 76 No Physical Data W-788 ¹H-NMR(CDCl₃) δ ppm: 1.05(3H, t, J=7.3), 2.58(2H, q, J=7.3), 2.77-2.98(2H, m), 3.13-3.35(2H, m), 3.51-3.65(4H, m), 5.09 (1H, d, J=12.2), 5.13(2H, s), 5.19(1H, d, J=12.2), 7.24-7.38 (9H, m) W-794 ¹H-NMR(CDCl₃) δ ppm: 1.07(3H, t, J=7.6), 2.60(2H, q, J=7.6), 2.76(1H, ddd, J=3.2, 6.3, 13.5), 2.89(1H, ddd, J=3.2, 6.3, 13.5), 3.15(1H, ddd, J=3.2, 6.3, 11.5), (1H, ddd, J=3.2, 6.3, 11.5), 3.54-3.62(4H, m), 3.79(3H, s), 5.09 and 5.17(each 1H, ABq, J=12.2), 5.10(2H, s), 6.84(2H, d, J=8.3), 7.24-7.35(7H, m) W-869 ¹H-NMR(CDCl₃) δ ppm: 1.09(3H, t, J=7.3), 2.63(2H, q, J=7.3), 2.79-2.95(2H, m), 3.20-3.30(2H, m), 3.54-3.70(4H, m), 3.80 (3H, s), 5.11(2H, s), 5.25(2H, s), 6.86(2H, d, J=8.6), 7.22-7.38 (6H, m) W-919 ¹H-NMR(CDCl₃) δ ppm: 1.06(3H, t, J=7.3), 2.59(2H, q, J=7.3), 2.84-2.93(2H, m), 3.20-3.34(2H, m), 3.53-3.67(4H, m), 3.80 (3H, s), 5.05(1H, d, J=12.2), 5.11(2H, s), 5.13(1H, d, J=12.2), 6.85(2H, d, J=8.6), 7.21-7.33(6H, m) W-944 ¹H-NMR(CDCl₃) δ ppm: 1.06(3H, t, J=7.3), 2.34(3H, s), 2.59 (2H, q, J=7.3), 2.75-2.93(2H, m), 3.19-3.31(2H, m), 3.54- 3.71(4H, m), 3.79(3H, s), 5.10(2H, s), 5.11(1H, d, J=12.2), 5.19(IH, d, J=12.2), 6.85(2H, d, J=8.6), 7.14-7.28(6H, m) W-994 ¹H-NMR(CDCl₃) δ ppm: 1.05(3H, t, J=7.3), 2.33(3H, s), 2.58 (2H, q, J=7.3), 2.76-2.95(2H, m), 3.15-3.33(2H, m), 3.52- 3.77(4H, m), 3.79(3H, s), 5.04(1H, d, J=12.2), 5.10(2H, s), 5.13(1H, d, J=12.2), 6.85(2H, d, J=8.6), 7.13(2H, d, J=7.9), 7.20(2H, d, J=7.9), 7.26(2H, d, J=8.6) W-1019 ¹H-NMR(CDCl₃) δ ppm: 1.07(3H, t, J=7.3), 2.60(2H, q, J=7.3), 2.81-2.98(2H, m), 3.22-3.34(2H, m), 3.52-3.65(4H, m), 3.80 (3H, s), 3.81(3H, s), 5.11(2H, s), 5.17(1H, d, J=12.2), 5.23(1H, d, J=12.2), 6.82-6.95(4H, m), 7.23-7.30(4H, m) W-1069 ¹H-NMR(CDCl₃) δ ppm: 1.04(3H, t, J=7.3), 2.57(2H, q, J=7.3), 2.83-2.91(2H, m), 3.24-3.31(2H, m), 3.56-3.68(4H, m), 3.80 (3H, s), 5.02(1H, d, J=12.2), 5.10(2H, s), 5.10(1H, d, J=12.2), 6.83-6.88(4H, m), 7.22-7.28(4H, m)

TABLE 77 No Physical Data W-1094 ¹H-NMR(CDCl₃) δ ppm: 1.07(3H, t, J=7.3), 2.60(2H, q, J=7.3), 2.86-2.94(2H, m), 3.24-3.33(2H, m), 3.52-3.69(4H, m), 3.79 (3H, s), 5.03(1H, d, J=12.8), 5.07(2H, s), 5.10(1H, d, J=12.8), 6.86(2H, d, J=8.6), 7.14(2H, d, J=8.6), 7.26(2H, d, J=8.6), 7.41 (2H, d, J=8.6) W-1144 ¹H-NMR(CDCl₃) δ ppm: 1.12(3H, t, J=7.6), 2.66(2H, q, J=7.6), 2.91(2H, m), 3.28(2H, m), 3.57(4H, m), 3.80(3H, s), 5.12(2H, s), 5.26 and 5.28(each 1H, ABq, J=13.7), 6.86(2H, d, J=8.8), 7.18-7.30(4H, m), 7.67(1H, dt, J=1.7, 7.6), 8.56(1H, d, J=4.2) W-1169 ¹H-NMR(CDCl₃) δ ppm: 1.06(3H, t, J=7.6), 2.59(2H, q, J=7.6), 2.83(2H, m), 3.24(2H, m), 3.51-3.70(4H, m), 3.80(3H, s), 5.11(2H, s), 5.12 and 5.17(each ABq, J=12.2), 6.85(2H, d, J=8.8), 7.24-7.30(3H, m), 7.63(1H, br d, J=7.8), 8.54-8.57 (2H, m) W-1194 mp 69.5-70.5° C. W-1240 ¹H-NMR(CDCl₃) δ ppm: 0.92(3H, t, J=7.6), 1.53(2H, m), 2.57 (2H, t, J=8.1), 2.78(1H, m), 2.86(1H, m), 3.15(1H, m), 3.26 (1H, m), 3.57(4H, m), 3.80(3H, s), 5.08 and 5.16(each 1H, ABq, J=12.4), 5.09(2H, s), 6.84(2H, d, J=8.8), 7.24-7.34(7H, m) W-1300 mp 73-74° C. W-1404 Isomer A: ¹H-NMR(CDCl₃) δ ppm: 1.20(6H, d, J=6.8), 2.70- 2.90(3H, br), 3.00(1H, sept, J=6.8), 3.22(2H, m), 3.33(2H, m), 3.61(1H, br), 3.80(3H, s), 5.02(2H, br s), 5.07(2H, s), 6.85 (2H, d, J=8.6), 7.24(2H, d, J=8.6), 7.29-7.37(5H, m) Isomer B: ¹H-NMR(CDCl₃) δ ppm: 1.22(6H, d, J=7.1), 2.69- 2.90(2H, m), 3.13-3.27(2H, m), 3.40(1H, sept, J=7.1), 3.50- 3.68(4H, m), 3.80(3H, s), 5.06 and 5.15(each 1H, ABq, J= 12.2), 5.09(2H, s), 6.85(2H, d, J=8.8), 7.26(2H, d, J=8.8), 7.28-7.36(5H, m) W-1494 ¹H-NMR(CDCl₃) δ ppm: 2.02(3H, s), 2.92-2.97(2H, m), 3.31- 3.35(2H, m), 3.62-3.68(6H, m), 3.80(3H, s), 4.97(1H, d, J=11.6), 5.05(1H, d, J=11.6), 5.10(2H, s), 6.63(2H, d, J=8.6), 6.85(2H, d, J=8.6), 7.12(2H, d, J=8.6), 7.26(2H, d, J=8.6)

TABLE 78 No Physical Data W-1504 ¹H-NMR(CDCl₃) δ ppm: 2.04(3H, s), 2.16(3H, s), 2.78-2.95 (2H, m), 3.21-3.34(2H, m), 3.57-3.66(4H, m), 3.80(3H, s), 5.05(1H, d, J=12.2), 5.13(1H, d, J=12.2), 5.10(2H, s), 6.85(2H, d, J=8.6), 7.19(1H, s), 7.23-7.28(4H, m) 7.46(2H, d, J=7.9), W-1534 ¹H-NMR(CDCl₃) δ ppm: 2.03(3H, s), 2.68-2.90(2H, m), 3.07- 3.25(2H, m), 3.56-3.63(4H, m), 3.79(3H, s), 5.09(2H, s), 5.50 (1H, d, J=12.2), 5.70(1H, d, J=12.2), 6.84(2H, d, J=8.5), 7.23(2H, d, J=8.5), 7.40-7.56(4H, m), 7.77-7.88(2H, m), 8.09(1H, m) W-1554 ¹H-NMR(CDCl₃) δ ppm: 2.04(3H, s), 2.98-3.02(2H, m), 3.31- 3.40(2H, m), 3.57-3.78(4H, m), 3.80(3H, s), 5.12(2H, s), 5.17 (2H, s), 6.77(1H, d, J=3.7), 6.84-6.98(3H, m), 7.24-7.29(3H, m) W-1564 ¹H-NMR(CDCl₃) δ ppm: 2.05(3H, s), 2.90-3.05(2H, m), 3.25- 3.42(2H, m), 3.55-3.75(4H, m), 3.80(3H, s), 5.11(2H, s), 5.14 (2H, s), 6.86(2H, d, J=8.8), 7.05(1H, dd, J=1.2 J=4.9), 7.22- 7.30(4H, m) W-1571 ¹H-NMR(CDCl₃) δ ppm: 2.06(3H, s), 2.83-3.92(2H, m), 3.15- 3.36(2H, m), 3.55-3.62(4H, m), 5.07(2H, s), 5.10 and 5.17 (each 1H, ABq, J=12.5), 6.74(2H, d, J=8.5), 7.12(2H, d, J= 8.5), 7.29-7.33(5H, m) W-1575 ¹H-NMR(CDCl₃) δ ppm: 2.06(3H, s), 2.80-2.99(2H, m), 3.13- 3.31(2H, m), 3.47(3H, s), 3.56-3.63(4H, m), 5.11(2H, s), 5.16 (2H, s), 5.11 and 5.17(each 1H, ABq, J=12.2), 6.98(2H, d, J= 8.5), 7.25(2H, d, J=8.5), 7.26-7.33(5H, m) W-1576 ¹H-NMR(CDCl₃) δ ppm: 2.07(3H, s), 2.85-2.96(4H, m), 3.13- 3.30(2H, m), 3.52-3.70(4H, m), 3.77(3H, s), 4.30-4.36(2H, m), 5.11 and 5.20(each 1H, ABq, J=12.2), 6.82(2H, d, J=8.5), 7.11(2H, d, J=8.5), 7.26-7.33(5H, m) W-1644 ¹H-NMR(CDCl₃) δ ppm: 1.08(3H, t, J=7.3), 2.62(2H, q, J=7.3), 2.76-2.97(2H, m), 3.12-3.34(2H, m), 3.51-3.66(4H, m), 3.80 (3H, s), 5.11(2H, s), 5.14(1H, d, J=12.8), 5.23(1H, d, J=12.8), 6.86(2H, d, J=8.6), 7.26(2H, d, J=8.6), 7.42(2H, d, J=7.9), 7.60 (2H, d, J=7.9)

TABLE 79 No Physical Data W-1654 ¹H-NMR(CDCl₃) δ ppm: 1.05(3H, t, J=7.3), 2.29(3H, s), 2.30 (3H, s), 2.58(2H, q, J=7.3), 2.76-2.94(2H, m), 3.20-3.29(2H, m), 3.32-3.70(4H, m), 3.79(3H, s), 5.06(1H, d, J=12.2), 5.10 (2H, s), 5.16(1H, d, J=12.2), 6.85(2H, d, J=8.6), 7.26(2H, d, J=8.6), 7.00-7.06(3H, m) W-1694 ¹H-NMR(CDCl₃) δ ppm: 1.06(3H, t, J=7.3), 2.59(2H, q, J=7.3), 2.86-2.94(2H, m), 3.27-3.33(2H, m), 3.60-3.68(4H, m), 3.80 (3H, s), 5.05-5.13(4H, m), 6.85(2H, d, J=8.6), 7.04(1H, d, J=4.9), 7.20-7.29(4H, m) W-1702 ¹H-NMR(CDCl₃) δ ppm: 1.07(3H, t, J=7.3), 1.41(3H, t, J=7.3), 2.60(2H, q, J=7.3), 2.70-2.95(2H, m), 3.10-3.32(2H, m), 3.56- 3.70(4H, m), 4.02(2H, q, J=7.3), 5.08(1H, d, J=12.2), 5.10 (2H, s), 5.18(1H, d, J=12.2), 6.84(2H, d, J=9.1), 7.22-7.33(7H, m) W-1703 ¹H-NMR(CDCl₃) δ ppm: 0.90-1.13(6H, m), 1.60-1.85(2H, m), 2.58-2.63(2H, m), 2.70-3.35(4H, m), 3.40-3.70(4H, m), 3.85- 4.12(2H, m), 5.05-5.25(4H, m), 6.80-6.93(2H, m), 7.21- 7.40(7H, m) W-1704 ¹H-NMR(CDCl₃) δ ppm: 1.06(3H, t, J=7.3), 2.29(3H, s), 2.59 (2H, q, J=7.3), 2.74-2.95(2H, m), 3.1l-3.33(2H, m), 3.54- 3.64(4H, m), 5.09(1H, d, J=12.2), 5.16(2H, s), 5.19(1H, d, J=12.2), 7.05(2H, d, J=8.6), 7.28-7.36(7H, m) Y-794 ¹H-NMR(CDCl₃) δ ppm: 1.07(3H, t, J=7.6), 2.15(2H, m), 2.54 (2H, m), 2.60(2H, q, J=7.6), 3.13(2H, m), 3.75(1H, m), 3.80 (3H, s), 3.96(1H, m), 5.08 and 5.17(each 1H, ABq, J=12.2), 5.10(2H, s), 6.85(2H, d, J=8.8), 7.24-7.34(7H, m) mp 105-110° C. b-594 ¹H-NMR(CDCl₃) δ ppm: 1.83-1.95(1H, m), 2.12(3H, s), 2.16 (3H, s), 2.10-2.25(2H, m), 2.27-2.40(1H, m), 2.95-3.02(2H, m), 3.50-3.83(2H, m), 3.80(3H s) 5.11(2H, s), 5.16(2H, d, J=3.7), 6.86(2H, d, J=8.6), 7.20(2H, d, J=6.1), 7.26(2H, d, J=8.6), 8.57(2H, d, J=6.1)

TABLE 80 No Physical Data b-794 ¹H-NMR(CDCl₃) δ ppm: 1.07(3H, t, J=7.6), 1.94-2.37(4H, m), 2.18(3H, s), 2.60(2H, q, J=7.6), 2.96(2H, m), 3.63(2H, m), 3.80(3H, s), 5.10(2H, s), 5.11 and 5.16(each 1H, ABq, J=12.5), 6.85(2H, d, J=8.6), 7.24-7.34(7H, m) b-1194 ¹H-NMR(CDCl₃) δ ppm: 1.12(3H, t, J=7.6), 1.87(1H, m), 2.15 (3H, s), 2.05-2.36(3H, m), 2.65(2H, q, J=7.6), 2.95(2H, m), 3.50-3.70(2H, m), 3.80(3H, s), 5.11(2H, s), 5.12 and 5.17 (each 1H, ABq, J=12.2) 6.85(2H, d, J=8.8), 7.19(2H, d, J=5.9), 7.25(2H, d, J=8.8), 8.56(2H, d, J=5.9) e-794 ¹H-NMR(CDCl₃) δ ppm: 1.07(3H, t, J=7.3), 1.28(3H, t, J=7.3), 2.61(2H, q, J=7.3), 2.67-3.81(8H, m), 3.79(3H, s), 4.15(2H, q, J=7.3), 5.04(1H, d, J=12.2), 5.09(2H, s), 5.17(1H, d, J=12.2), 6.85(2H, d, J=8.6), 7.22-7.30(7H, m) f-794 ¹H-NMR(CDCl₃) δ ppm: 1.07(3H, t, J=7.3), 2.03-2.70(4H, m), 2.60(2H, q, J=7.3), 2.90-3.10(2H, m), 3.06(2H, s), 3.50-3.80 (2H, m), 3.71(3H, s), 3.80(3H, s), 5.10(2H, s), 5.10(1H, d, J=12.8), 5.18(1H, d, J=12.8), 6.85(2H, d, J=9.2), 7.24-7.33 (7H, m) g-794 mp 107-112° C. h-794 ¹H-NMR(CDCl₃) δ ppm: 1.10(3H, t, J=7.3), 2.55(3H, s), 2.56- 3.90(8H, m), 2.63(2H, q, J=7.3), 3.79(3H, s), 5.08(1H, d, J=12.2), 5.11(2H, s), 5.18(1H, d, J=12.2), 6.85(2H, d, J=8.6), 7.23-7.33(7H, m) i-794 mp 89.5-91° C. j-794 ¹H-NMR(CDCl₃) δ ppm: 1.07(3H, t, J=7.6), 2.08(2H, m), 2.61 (2H, q, J=7.6), 3.45(2H, br s), 3.68(2H, m), 3.79(3H, s), 5.12 (2H, s), 5.14(2H, s), 6.85(2H, d, J=8.5), 7.27(2H, d, J=8.5), 7.29-7.32(5H, m) k-794 ¹H-NMR(CDCl₃) δ ppm: 1.06 and 1.07(total 3H, t, J=7.6), 1.49-1.89(2H, m), 2.19 and 2.25(total 3H, s), 2.23-2.31(2H, m), 2.45-2.53(4H, m), 2.84-3.08(2H, m), 3.55-3.74(2H, m), 3.79(3H, s), 5.08-5.20(4H, m), 6.85(2H, d, J=8.6), 7.25- 7.30(7H, m)

TABLE 81 No Physical Data l-1 ¹H-NMR(CDCl₃) δ ppm: 2.13(3H, s), 2.90(3H, s), 3.07(3H, s), 3.29(3H, s), 3.99(3H, s), 6.90-7.02(3H, m), 7.23-7.29(2H, m). n-776 mp 89-92° C. n-785 ¹H-NMR(CDCl₃) δ ppm: 1.07(3H, t, J=7.6), 2.63(2H, q, J=7.6), 2.94(2H, t, J=4.9), 3.29(2H, t, J=4.9), 3.59(4H, brs), 4.45(2H, d, J=4.9), 5.10(2H, s), 6.24(1H, t, J=4.9), 7.22-7.40(10H, m) n-794 ¹H-NMR(CDCl₃) δ ppm: 1.08(3H, t, J=7.6), 2.63(2H, q, J=7.6), 2.94(2H, t, J=4.9), 3.29(2H, t, J=4.9), 3.59(4H, brs), 3.79(3H, s), 4.38(2H, d, J=4.9), 5.10(2H, s), 6.15(1H, t, J=4.9), 6.84(2H, d, J=8.5), 7.19(2H, d, J=8.5), 7.32(5H, m) n-1456 ¹H-NMR(CDCl₃) δ ppm: 1.18(3H, t, J=7.6), 2.77(2H, q, J=7.6), 3.01(2H, t, J=4.9), 3.35(2H, t, J=4.9), 3.60-3.75(4H, m), 5.15 (2H, s), 6.93(1H, t, J=7.3), 7.08(2H, d, J=7.9), 7.25-7.40(7H, m), 8.28(1H, s) n-1461 ¹H-NMR(CDCl₃) δ ppm: 1.17(3H, t, J=7.6), 2.74(2H, q, J=7.6), 2.99(2H, t, J=4.9), 3.34(2H, t, J=4.9), 3.60-3.72(4H, m), 5.15 (2H, s), 6.87-6.92(2H, m), 7.12-7.20(2H, m), 7.27-7.44 (5H, m), 8.34(1H, s) n-1466 ¹H-NMR(CDCl₃) δ ppm: 1.16(3H, t, J=7.6), 2.74(2H, q, J=7.6), 3.00(2H, t, J=4.9), 3.35(2H, t, J=4.9), 3.67(4H, brs), 5.15(2H, s), 7.10(2H, d, J=8.5), 7.22(2H, d, J=8.5), 7.35(5H, m), 8.30 (1H, s) n-1476 ¹H-NMR(CDCl₃) δ ppm: 1.17(3H, t, J=7.6), 2.29(3H, s), 2.76 (2H, q, J=7.6), 3.01(2H, t, J=4.9), 3.35(2H, t, J=4.9), 3.60-3.72 (4H, m), 5.14(2H, s), 6.98(2H, d, J=8.5), 7.07(2H, d, J=8.5), 7.27-7.42(5H, m), 8.21(1H, s) n-1486 ¹H-NMR(CDCl₃) δ ppm: 1.17(3H, t, J=7.6), 2.75(2H, q, J=7.6), 3.02(2H, t, J=4.9), 3.35(2H, t, J=4.9), 3.64-3.75(4H, m), 3.78 (3H, s), 5.14(2H, s), 6.85(2H, d, J=9.2), 7.02(2H, d, J=9.2), 7.25-7.42(5H, m), 8.21(1H, s)

TABLE 82 No Physical Data o-794 ¹H-NMR(CDCl₃) δ ppm: 1.07(3H, t, J=7.6), 2.65(2H, q, J=7.6), 2.84(3H, s), 2.92-2.98(2H, m), 3.23-3.69(6H, m), 3.79(3H, s), 4.32(1H, d, J=14.3), 4.36(1H, d, J=14.3), 5.05(1H, d, J=12.5), 5.15(1H, d, J=12.5), 6.84(2H, d, J=8.5), 7.18(2H, d, J=8.5), 7.33(5H, m) o-799 mp 97-98° C. o-1486 ¹H-NMR(CDCl₃) δ ppm: 1.15(3H, t, J=7.3), 2.74(2H, q, J=7.3), 2.97-3.20(2H, m), 3.24-3.36(1H, m), 3.38-3.52(2H, m), 3.45 (3H, s), 3.57-3.64(2H, m), 3.67-3.80(1H, m), 3.79(3H, s), 5.08(1H, d, J=12.2), 5.19(1H, d, J=12.2), 6.86(2H, d, J=9.2), 7.17(2H, d, J=9.2), 7.27-7.42(5H, m) p-794 ¹H-NMR(CDCl₃) δ ppm: 1.11(3H, t, J=7.3), 1.90-2.05(1H, m), 2.49(3H, s), 2.50-3.02(6H, m), 3.30-3.46(2H, m), 3.68-3.82 (1H, m), 3.77(3H, s), 4.90(1H, d, J=17.4), 5.08(1H, d, J=12.5), 5.22(1H, d, J=12.5), 5.57(1H, d, J=17.4), 6.80-6.93(4H, m), 7.25-7.40(5H, m) q-776 mp 105-106° C. q-794 ¹H-NMR(CDCl₃) δ ppm: 0.80(3H, t, J=7.3), 2.23-2.42(3H, m), 2.52-2.65(1H, m), 2.95-3.15(3H, m), 3.42(2H, t, J=4.9), 3.62- 3.75(1H, m), 3.78(3H, s), 5.02-5.50(4H, m), 6.86(2H, d, J=8.5), 7.06(2H, d, J=8.5), 7.25-7.45(9H, m), 7.57(2H, dd, J=1.8, 7.9) t-794 ¹H-NMR(CDCl₃) δ ppm: 1.08(3H, t, J=7.3), 2.11(2H, t, J=4.9), 2.20(3H, s), 2.32(2H, t, J=4.9), 2.63(2H, q, J=7.3), 3.07(2H, t, J=4.9), 3.64(2H, t, J=4.9), 3.79(3H, s), 4.38(2H, d, J=4.9), 5.10 (2H, s), 6.11(1H, t, J=4.9), 6.84(2H, d, J=8.5), 7.27-7.40(5H, m) v-794 ¹H-NMR(CDCl₃) δ ppm: 1.09(3H, t, J=7.6), 2.63(2H, q, J=7.6), 2.95-3.30(4H, m), 3.66(2H, m), 3.80(3H, s), 4.16(2H, m), 5.06 and 5.16(each 1H, ABq, J=12.2), 5.12(2H, s), 6.84(2H, d, J=8.8), 7.25-7.33(7H, m) x-10 ¹H-NMR(CDCl₃) δ ppm: 1.99(3H, s), 3.86(3H, s), 3.94(3H, s), 5.21(2H, s), 7.33(5H, m)

TABLE 83 No Physical Data x-185 ¹H-NMR(CDCl₃) δ ppm: 2.01(3H, s), 3.83(3H, s), 5.15(2H, s), 5.21(2H, s), 7.33(10H, m) x-480 mp 53-54° C. y-476 ¹H-NMR(CDCl₃) δ ppm: 1.28(3H, t, J=7.3), 2.05(3H, s), 3.98 (3H, s), 4.31(2H, q, J=7.3), 5.08(2H, s), 7.15(1H, dd, J=8.8, 2.0), 7.40-7.42(4H, m) z-10 mp 88-89° C. z-185 mp 79-80° C. z-476 mp 134-136° C. z-480 mp 111-112° C.

Agrochemical Formulations

Formulation 1

A mixture of 2 parts by weight of Compound C-180 and 98 parts by weight of talc was pulverized to obtain a powder formulation.

Formulation 2

40 Parts by weight of Compound C-180, 10 parts by weight of sodium lignosulfonate and 50 parts by weight of water were mixed to obtain a suspension formulation.

Pharmaceutical Formulations

Formulation for Injection

5 g of Compound b-251 was dissolved in 10 L of distilled water for injection to form a solution for injection, which was then dispensed into 100 ampoules.

The following Test Examples illustrate the fungicidal effects of the compound according to the present invention.

[Controlling effects on various plant diseases by foliage application (pot experiment)]

Experimental Method

A test compound was dissolved in a small amount of N,N-dimethylformamide, and the solution was diluted to a given concentration with distilled water containing a spreader, whereby preparing a liquid sample. The liquid sample was sprayed to each test plant, and after 24 hours each pathogens was inoculated by the method described below.

A % control was calculated according to the following equation. ${\% \quad {Control}} = {{100} \times \frac{\begin{matrix} \left( {{{Severity}\quad {and}\quad {number}\quad {of}\quad {lesions}\quad {in}\quad {untreated}\quad {plot}} -} \right. \\ \left. {{Severity}\quad {and}\quad {number}\quad {of}\quad {lesions}\quad {in}\quad {treated}\quad {plot}} \right) \end{matrix}}{\left( {{Severity}\quad {and}\quad {number}\quad {of}\quad {lesions}\quad {in}\quad {untreated}\quad {plot}} \right)}}$

Test Example 1

Controlling effect on rice blight (Pyricularia oryzae)

A two-week rice seedling (cv.: AICHIASAHI) was transplanted in a plastic cup which was 9 cm in diameter and cultivated for 2 weeks, and then the test compound in the form of a solution or a suspension was sprayed to the foliage of the rice seedling. A conidia suspension of a rice blight microorganism (Pyricularia oryzae) cultured in an oatmeal medium was inoculated by spraying, and after the inoculation the test plant was kept in a moist chamber (28° C., 100% RH) for 24 hours, and subsequently cultivated in a green house for 5 days. Six days after the inoculation, the number of the lesions on the leaves of the inoculated plant was measured to calculate the % control.

The results are shown below.

Controlling effect on rice blight (Pyricularia oryzae) by foliage Compound No. application at 500 ppm (% control) C-11 90 C-86 90 C-95 90 C-96 90 Reference agent: Fthalide 97

Test Example 2

Controlling effect on cucumber mildew microorganism (Sphaerotheca fuliginea)

A seed of a cucumber (cv.: TSUKUBASHIROIBO) was sown in a plastic cup which was 9 cm in diameter, and cultivated for 2 to 3 weeks. The liquid test sample in the form of a solution or suspension was sprayed on the surface of the first leaf. The pathogen was inoculated to the leaf by spraying a conidia suspension of a cucumber mildew microorganism (Sphaerotheca fuliginea) which had been cultured on a cucumber leaf. After the inoculation, the plant was kept in a greenhouse at 20° C. for 10 days. Then, the infected area on the leaf was observed, and the % control was calculated.

The results are shown below.

Controlling effect on cucumber mildew microorganism (Sphaerotheca fuliginea) by foliage Compound No. application at 500 ppm (% control) B-476 100 C-180 100 C-780 97 F-180 100 Reference agent: Fenarimol 100

Test Example 3

Controlling Effect on Wheat Powdery Mildew Microorganism (Erysiphe graminis f.sp.tritici)

A seed of a wheat (cv.: NORIN No.61) was sown in a plastic cup which was 9 cm in diameter and cultivated for 2 to 3 weeks. The test compound in the form of a solution or suspension was sprayed to a seedling, and conidia of a wheat powdery mildew microorganism (Erysiphe graminis fsp.tritici) cultured on a wheat leaf was dropped on the test plant to inoculate the plant with the pathogen. After the inoculation, the plant was kept in a green house at 20° C. for 10 days. The infected area on the leaf was observed, and the % control was calculated.

The results are shown below.

Controlling effect on wheat powdery mildew microorganism (Erysiphe graminis f.sp.tritici) Compound No. by foliage application at 500 ppm (% control) C-11  90 C-86  90 C-96  90 C-176 90 C-180 90 C-251 90 C-276 90 C-780 90 F-180 90 Reference agent: Fenarimol 97

The tachykinin receptor antagonistic effect of a compound according to the present invention was investigated by the method described below.

[Effect of compound on capsaicin-induced increase in blood vessel permeability]

Method

5 Minutes after giving Evans Blue (30 mg/kg, i.v.) to a guinea pig anesthetized with pentobarbital (30 mg/kg, i.p.), a test compound dissolved in dimethylsulfide was injected intravenously. After further 5 minutes, capsaicin (0.15 mg/kg, i.v.) was given to induce the plasma transudation. 5 Minutes after administration of capsaicin, the guinea pig was sacrificed to isolate the trachea and the urinary bladder. After extraction with formamide for 24 hours, the dye content in each tissue was quantified on the basis of the absorbance at 620 nm, and the amount of the dye transudated into the tissue was calculated from the calibration curve.

By the method described above, the amount of the compound required to obtain 50% suppression (ED₅₀) was determined and represented in units (mg/kg).

ED₅₀ (mg/kg) Compound No. Guinea pig trachea Guinea pig urinary bladder M-11  0.024 M-86  0.085 W-96  0.040 W-176 0.145 0.075 b-180 0.054 0.087 b-251 0.017 0.017

Industrial Applicability

A compound according to the present invention is useful as a fungicide, especially as an agricultural fungicide. It also has a tachykinin receptor antagonistic effect, and thus is useful as a pharmaceutical. 

What is claimed is:
 1. A compound represented by Formula (I):

wherein R¹ is an optionally substituted aryl, an optionally substituted alkyl or an optionally substituted cycloalkyl; R² is an optionally substituted alkyl, an optionally substituted cycloalkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted alkylsulfonyl, an optionally substituted aryl, an optionally substituted arylsulfonyl or an optionally substituted heterocyclic group; R³ is an optionally substituted alkyl, an optionally substituted cycloalkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted alkylsulfonyl, an optionally substituted aryl, an optionally substituted arylsulfonyl or an optionally substituted heterocyclic group; R⁴ and R⁵ are the same or different from each other and each is a hydrogen atom, an optionally substituted alkyl, an optionally substituted cycloalkyl or an optionally substituted alkoxy, or R⁴ and R⁵ may be taken together with their adjacent nitrogen atom to form an optionally substituted monocyclic ring or polycyclic ring; X and Y are the same or different from each other and each is an oxygen atom or an NR⁶ wherein R⁶ is a hydrogen atom, an optionally substituted alkyl, an optionally substituted aryl, an optionally substituted alkanoyl or an optionally substituted aroyl; Z is an oxygen atom or a sulfur atom; a wave-shaped line (˜) represents the configuration of an E form or a Z form or a mixture thereof; provided that when R² is an optionally substituted benzyl then the substituent is not a group represented by formula:

wherein (R¹²)₂ is H₂, ═O, ═CH—OH, ═CHOCH₃, ═N—OH or ═N—OCH₃; and R¹³ represents an alkoxy or a monoalkylamino; and a salt or a hydrate thereof.
 2. A compound or a salt or a hydrate thereof according to claim 1 wherein R¹ is an aryl or an alkyl; R² is an optionally substituted alkyl, alkenyl, alkynyl, aryl or heterocyclic group; R³ is an optionally substituted alkyl, alkenyl, alkynyl, an optionally substituted aryl, an optionally substituted arylsulfonyl or heterocyclic group; R⁴ and R⁵ are the same or different from each other and each is a hydrogen atom, an alkyl or an alkoxy, or R⁴ and R⁵ may be taken together with their adjacent nitrogen atom to form an optionally substituted monocyclic ring; X and Y are the same or different from each other and each is an oxygen atom or a NR⁶ wherein R⁶ is a hydrogen atom, alkyl, aryl, alkanoyl or aroyl.
 3. A compound or a salt or a hydrate thereof according to claim 1 wherein R¹ is methyl, ethyl, propyl, isopropyl or an optionally substituted phenyl.
 4. A compound or a salt or a hydrate thereof according to claim 1 wherein R² is methyl, methoxymethyl, ethyl, allyl, cinnamyl, 2-propynyl, 2-butynyl, 2-pyridyl, an optionally substituted phenyl, an optionally substituted benzyl, an optionally substituted 2-pyridylmethyl, an optionally substituted 3-pyridylmethyl, an optionally substituted 4-pyridylmethyl, an optionally substituted 2-thenyl or an optionally substituted 3-thenyl.
 5. A compound or a salt or a hydrate thereof according to claim 1 wherein R³ is methyl, ethyl, propyl, isopropyl, allyl, cinnamyl, 2-propynyl, 2-butynyl, 2-pyridyl, an optionally substituted benzyl, an optionally substituted 2-phenylethyl, an optionally substituted 2-pyridylmethyl, an optionally substituted 3-pyridylmethyl, an optionally substituted 4-pyridylmethyl or an optionally substituted benzenesulfonyl.
 6. A compound or a salt or a hydrate thereof according to claim 1 wherein —NR⁴R⁵ is —NH₂, —NHMe, —NMe₂, —NEt₂, —N(Me)Et, —N(OMe)Me, an optionally substituted 1-pyrrolidinyl, an optionally substituted piperidino, an optionally substituted morpholino, an optionally substituted 4-thiomorpholinyl, an optionally substituted 1-piperazinyl, an optionally substituted 2-oxazolanyl or an optionally substituted diazepan-1-yl.
 7. A compound or a salt or a hydrate thereof according to claim 1 wherein X is an oxygen atom, —NH—, —N(Me)— or —N(Ph)—.
 8. A compound or a salt or a hydrate thereof according to claim 1 wherein Y is an oxygen atom, —NH—, —N(Me)—, —N(Et)—, —NP(h)—, —N(Ac)— or —N(Bz)—.
 9. A pharmaceutical composition containing as an active ingredient a compound according to claim
 1. 10. An agrochemical composition, comprising a compound of claim 1 and an agrochemically-acceptable carrier or diluent.
 11. A fungicide composition, comprising a compound of claim 1 and a fungicidally-acceptable carrier or diluent.
 12. A tachykinin receptor antagonist composition, comprising a compound of claim 1 and a pharmaceutically-acceptable carrier or diluent.
 13. A substance P receptor antagonist composition, comprising a compound of claim 1 and a pharmaceutically-acceptable carrier or diluent.
 14. A compound represented by Formula (II):

wherein R⁷ is a hydrogen atom or alkyl, R¹ is an optionally substituted aryl, an optionally substituted alkyl or an optionally substituted cycloalkyl; R² is an optionally substituted alkyl, an optionally substituted cycloalkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted alkylsulfonyl, an optionally substituted aryl, an optionally substituted arylsulfonyl or an optionally substituted heterocyclic group; R³ is an optionally substituted alkyl, an optionally substituted cycloalkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted alkylsulfonyl, an optionally substituted aryl, an optionally substituted arylsulfonyl or an optionally substituted heterocyclic group; X is an oxygen or an NR⁶ wherein R⁶ is a hydrogen atom, alkyl, aryl, alkanoyl or aroyl; provided that when R² is optionally substituted benzyl then the substituent is not a group represented by Formula:

wherein (R¹²)₂ is H₂, ═O, ═CH—OH, ═CHOCH₃, ═N—OH or ═N—OCH₃; R¹³ is alkoxy or monoalkylamino; and at least one of R¹, R³ and R⁷ is not methyl. 